Shokoofe Noori; Zuhair Mohammad Hassan; Omid Salehian
Volume 10, Issue 1 , March 2013, , Pages 10-21
Abstract
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on ...
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Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects on reducing the tumor volume and shifting the cytokine profile were investigated. We also assessed if intraperitoneally injected Sclareol could improve the outcome of cancer therapy through suppressing the regulatory T cells. Results: The results confirmed a significant decrease in the tumor size. Furthermore, a significant decrease in the level of IL-4 and an increase in the level of IFN-γ were noticed in the intraperitoneally injected Sclareol group (p<0.05). It was also observed that the splenocytes of treated animals significantly increase in cell proliferation assay. Moreover, measurements of splenic T regulatory cell indicated that intraperitoneally injected Sclareol significantly decreased the number of splenic T regulatory cell. Conclusion: Our results suggest that Sclareol, by reducing T-reg cells frequency and also tumor size can enhance the effect of cancer therapy as an immunostimulant.
Lida Toomarian; Mandana Sattari; Nazanin Hashemi; Nikoo Tadayon; Alireza Akbarzadeh Baghban
Abstract
Background: The infectious nature of severe early-childhood caries (S-ECC) points to the possible participation of immunologic host responses including neutrophils and their antimicrobial products. Objectives: The aim of this study was to determine the neutrophil apoptosis, α-defensins (HNP1-3) ...
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Background: The infectious nature of severe early-childhood caries (S-ECC) points to the possible participation of immunologic host responses including neutrophils and their antimicrobial products. Objectives: The aim of this study was to determine the neutrophil apoptosis, α-defensins (HNP1-3) and calprotectin levels in the saliva of preschool children and the association with S-ECC. Methods: Oral examinations were performed on 87 children aged 3-5 years and non stimulated whole saliva samples were collected. Thirty of these subjects were considered S-ECC children, 30 with moderate caries (MC) and 27 were caries free (CF). To detect apoptosis, cell staining was done with Annexin-V-Fluos and propidium iodide, and they were analyzed by fluorescent microscopy. The concentration of α-defensins and calprotectin were assessed using ELISA. Results: There were no statistical differences between groups considering the HNP1-3 or calprotectin salivary levels (p=0.06 and p=0.23, respectively). The HNP1-3 and calprotectin levels were negatively correlated and the correlation was significant in MC group (p=0.03). Lower levels of apoptotic neutrophils were obtained from CF subjects as compared with S-ECC children (p=0.03). Conclusions: Our findings establish that apoptotic mechanisms could be implicated in the immunity responses associated with S-ECC. We cannot yet
Yousef Nikmanesh; Mohammad Hossein Karimi; Ramin Yaghobi; Sayed Mahdi Marashi; Mahmood Mahmoudi; Ali Moravej; Shohreh Shahmahmoodi
Iraj Pakzad; Abbas Rezaee; Mohammad Javad Rasaee; Bahman Tabbaraee; Ali Delpisheh
Volume 6, Issue 1 , March 2009, , Pages 12-21
Abstract
Background: The immunogenic Brucella abortus ribosomal protein L7/L12 is a promising candidate antigen for the development of subunit vaccines against brucellosis. Objective: This study was aimed to evaluate the protection of recombinant Human Serum Albumin (HAS)-L7/L12 fusion protein in Balb/c mice. ...
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Background: The immunogenic Brucella abortus ribosomal protein L7/L12 is a promising candidate antigen for the development of subunit vaccines against brucellosis. Objective: This study was aimed to evaluate the protection of recombinant Human Serum Albumin (HAS)-L7/L12 fusion protein in Balb/c mice. Methods: The amplified L7/L12 gene was cloned in pYHSA5 vector, pYHSA5-L7/L12 construct was transformed in Saccharomyces cerevisiae and the expressed protein from supernatant was purified by affinity chromatography. Balb/c mice were immunized in five groups by tHSA-L7/L12 fusion protein (group 1), Brucella abortus S19 (group 2), HSA (group 3), recombinant L7/L12 (group 4), PBS (group 5). ELISA to detect antibody production, LTT test to assess antigen specific lymphocyte response were conducted prior to virulent B. abortus strain 544 challenge two weeks after the last injection. Bacterial counts from spleens of immunized mice were done four weeks after challenge. Results: In ELISA tests, the specific antibodies exhibited a dominance of immunoglobulin IgG1 over IgG2a. In addition, the tHSA-L7/L12 fusion protein and L7/L12 elicited a strong T-cell proliferative response upon restimulation in vitro with recombinant tHSA-L7/L12 and L7/L12, suggesting the induction of a cellular immunity response in vivo. However, there was no significant difference in proliferative response of L7/L12 and tHSA-L7/L12 fusion protein (p>0.05). The L7/L12 and tHSA-L7/L12 fusion protein vaccines could also induce significant protection against challenge with the virulent strain B. abortus 544 in Balb/c mice (p≤0.05). Conclusion: The tHSA-L7/L12 fusion protein, similar to L7/L12 has the ability to induce antigen specific lymphocyte proliferation, stimulate humoral immunity and engender protection.
Behrouz Gharesi-Fard; Rahil Askarinejad-Behbahani; Shabnam Behdin
Volume 11, Issue 1 , March 2014, , Pages 13-20
Abstract
Background: Miscarriage is a common phenomenon complicating more than half of pregnancies. Recurrent Pregnancy Loss (RPL) is defined as three or more pregnancies lost before the twentieth week of gestation. It is believed that abnormality in maternal immune reaction to fetus and sharing of HLA antigens ...
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Background: Miscarriage is a common phenomenon complicating more than half of pregnancies. Recurrent Pregnancy Loss (RPL) is defined as three or more pregnancies lost before the twentieth week of gestation. It is believed that abnormality in maternal immune reaction to fetus and sharing of HLA antigens might be associated with RPL. Objective: To investigate the effect of HLA-DRB1 sharing between the couples with recurrent pregnancy loss on the pregnancy outcome after leukocyte therapy. Methods: Sixty primary RPL women who were immunized and followed after therapy (30 successful and 30 unsuccessful) and their husbands formed the cases of this study. In addition, one hundred healthy women were considered as the controls. HLA-DRB1 genotypes of all the cases and controls were checked by PCR-SSP method. Results: HLA typing indicated that the prevalence of HLA-DRB1 sharing (defined as at least one allele sharing) between the couples with unsuccessful outcomes was significantly higher compared to those with successful outcomes (63.3% vs. 23.3%, p<0.004). Moreover, HLA DRB1*07:01 allelic group was significantly more frequent in the patients with unsuccessful outcome compared to the controls (18.3% vs. 8%, p<0.04). Conclusion: Our results confirmed the role of HLA sharing in RPL and revealed that HLA-DRB1 typing may be a valuable prognostic factor for the leukocyte therapy outcome.
Saeed Daneshmandi; Mohammad Hossein Karimi; Ali Akbar Pourfathollah
Volume 14, Issue 1 , March 2017, , Pages 13-23
Abstract
Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and ...
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Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and dendritic cells (DCs) and their modulatory effect on the immune response. Methods: MSCs and DCs were generated from bone marrow of Balb/c mice and T cells were generated from mice lymph nodes. TGF-β1 expressing lentiviruses were used for MSCs transduction, and then these engineered MSCs were co-cultured with T cells and DCs. T cells proliferation and cytokines release and also DCs maturation, TNF-α release, and stimulation of allogeneic T cells were evaluated. Results: T cells proliferation and IFN-γ release were suppressed by TGF-β1/MSCs while IL-4 secretion was enhanced. Co-cultured DCs with TGF-β1/MSCs showed reduced expression of CD40, CD86, and MHC II and also lower level of TNF-α secretion. Co-cultured DCs could also induce lower levels of allogeneic T cells proliferation and IFN-γ release in comparison to control DCs. Conclusion: Engineered TGF-β1/MSC cells showed collaborative immune suppressive functions between TGF-β1 and MSCs to modulate T cells and DCs immune responses. We therefore suggest that TGF-β1/MSC cells could provide a promising tool for treatment of clinical conditions such as organ transplantation, GVHD, and autoimmune disorders.
Elham Abdi; Hamid Najafipour; Siyavash Joukar; Shahriar Dabiri; Saeed Esmaeli-Mahani; Elham Abbasloo; Nasrin Houshmandi; Abbas Afsharipour
Volume 15, Issue 1 , March 2018, , Pages 14-27
Abstract
Background: IGF-1 and certain other cytokines have been shown to exert inflammatory/anti-inflammatory roles in chronic joint diseases. Objective: To assess the effect of IGF-1, IL-27 and IL-35, their interaction and their receptor expression in a rheumatoid arthritis model. Methods: Freund’s adjuvant-induced ...
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Background: IGF-1 and certain other cytokines have been shown to exert inflammatory/anti-inflammatory roles in chronic joint diseases. Objective: To assess the effect of IGF-1, IL-27 and IL-35, their interaction and their receptor expression in a rheumatoid arthritis model. Methods: Freund’s adjuvant-induced chronic joint inflammation was operated on 160 male rats. Animals were divided into histopathology and receptor expression groups, each composed of 10 subgroups including; control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL-27 antagonist and IGF-1+IL-35 antagonist. After two weeks, vehicle or agonist/antagonists were injected into the joint space every other day until day 28 where joint histopathology was performed. The expression of IGF-1, IL-27 and IL-35 receptors were assessed by western blot analysis. Results: IGF-1 did not show pro- or anti- inflammatory functions; endogenous IL-27 and IL-35, on the other hand, exerted inflammatory effects. IL-27 and IL-35 antagonists exerted the highest anti-inflammatory effects. The total inflammation scores were 0.55 ± 0.06, 4.63 ± 0.40, 3.63 ± 0.60, 2.50 ± 0.38 and 1.63 ± 0.40 regarding control, vehicle, IGF-1 Ant., IL-27 Ant. and IL-35Ant., respectively. IGF-1 receptor expression was reduced in chronic joint inflammation and all three antagonists augmented the IGF-1 receptor expression. IL-27 and IL-35 receptors were up-regulated by chronic joint inflammation. Conclusion: Overall, the results demonstrated the pro-inflammatory role of endogenous IL-27 and IL-35 along with the over expression of their receptors in chronic joint inflammation. IL-27 and IL-35 antagonists exerted the most anti-inflammatory effects and increased IGF-1 receptor expression. These two antagonists may be potential agents for new treatment strategies in chronic joint inflammatory diseases.
Meiling Hou; Xiaodong Wang; Jike Lu; Xun Guo; Cong Ding; Taotao Liang; Zhenyu Ji; Peng Xie; Xin Liu; Qiaozhen Kang
Abstract
Background: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination. ...
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Background: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination. Objective: To improve the efficacy of dendritic cell-based vaccines by the adjuvant activity of Helicobacter pylori neutrophil activating protein (HP-NAP), which is a virulence factor of Helicobacter pylori, has been proved as a TLR agonist with effective immunomodulatory activity. Methods: The recombinant HP-NAP (rHP-NAP) was expressed by using prokaryotic expression system. Dendritic cells (DCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After treating with rHP-NAP, the maturation of DCs and dendritic cell-based vaccine were assayed by using flow cytometry and qRT-PCR. The activation and proliferation of T cells were measured by FCM, ELISA and MTT methods. The tumor specific cytotoxic response to resistant B16F10 was detected by using lactate dehydrogenase-release assay and qRT-PCR. Results: The recombinant HP-NAP (rHP-NAP), prepared from E. coli prokaryotic expression system, was able to significantly promote the maturation of dendritic cell-based vaccine loaded with tumor cell lysate (TCL) of B16F10 (DC-B16F10-TCL). Furthermore, it effectively induced the activation and proliferation of T cells and tumor specific cytotoxic response to resistant B16F10 melanoma tumor cells. Conclusion: These results suggested that rHP-NAP possesses the potential for use as an adjuvant of dendritic cell-based vaccine in anti-melanoma treatment.
Hossein Asgarian Omran; Mahdi Shabani; Tahereh Shahrestani; Abdolfattah Sarafnejad; Jalal Khoshnoodi; Parvaneh Vossough; Mohammad Faranoush; Ramzan A. Sharifian; Mahmood Jeddi-Tehrani; Hodjatallah Rabbani; Fazel Shokri
Volume 4, Issue 1 , March 2007, , Pages 15-25
Abstract
Background: Immunophenotypic characterization of the leukemic cells has been widely used as a tool for diagnosis, classification, stratification and prognosis of leukaemia. Objective: To investigate the immunophenotypic subtype profiles of Iranian patients with acute lymphoblastic leukemia (ALL) and ...
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Background: Immunophenotypic characterization of the leukemic cells has been widely used as a tool for diagnosis, classification, stratification and prognosis of leukaemia. Objective: To investigate the immunophenotypic subtype profiles of Iranian patients with acute lymphoblastic leukemia (ALL) and its association to disease outcome. Methods: In this study, a total of 60 Iranian patients with ALL were immunophenotyped by flow cytometry using a panel of monoclonal antibodies specific for CD2, CD3, CD5, CD10, CD13, CD14, CD19, CD20, CD33, CD34, CD45, HLA-DR and TdT molecules. Results: The samples were initially categorized into T-ALL (n=9), B-ALL (n=50) and mixed lineage (n=1) based on the expression patterns of CD3 and CD19 molecules. B-ALL patients could further be classified into four subtypes, including Pro-B (n=7, 11.7%), Pre-B I (n=28, 46.7%), Pre-B II (n=13, 21.7%) and immature/mature B cells (n=2, 3.3%) on the basis of expression of CD10, CD19, CD20, HLA-DR and TdT. Clinical manifestations and laboratory findings of the patients did not reveal association with immunophenotypic sub-types of ALL, with the exception of mediastinal mass and WBC count at the time of diag-nosis which were found to be significantly higher in patients with T-ALL compared with B-ALL (p=0.001 and 0.014), respectively. Conclusion: Our results indicate that overall the immunophenotypic profile of Iranian ALL patients is similar to previous reports and it might be used for monitoring of minimal residual disease and prognosis.
Zeynab Aliyari; Forogh Alemi; Balal Brazvan; Hamid Tayefi Nasrabadi; Hojjatollah Nozad Charoudeh
Volume 12, Issue 1 , March 2015, , Pages 16-26
Abstract
Background: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell transplantation (HSCT), used in Leukemia treatment. CD26+ cells, a fraction of CD34 positive cells, are a major population of UCB cells which negatively regulate the in vivo homing and engraftment of HSCs. CD26 ...
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Background: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell transplantation (HSCT), used in Leukemia treatment. CD26+ cells, a fraction of CD34 positive cells, are a major population of UCB cells which negatively regulate the in vivo homing and engraftment of HSCs. CD26 is highly expressed in various cells such as HSCs, immune cells, fibroblasts, and epithelial cells. It has been shown that the inhibition of the CD26 on CD34+ cells improves the efficiency of Hematopoietic Stem and Progenitor Cell (HPC) transplantation. Objective: To evaluate the relationship between the production of B, T, and NK cells from the CD26 positive fraction of cord blood mononuclear cells. Methods: Cord blood mononuclear cells were cultured for 21 days using different combinations of stem cell factors (SCF), Flt3 ligand (FL), IL-2, IL- 7, and IL-15. The harvested cells were then analyzed by flowcytometry every week for 21 days. Results: T cell differentiation from CD26 subset of cord blood mononuclear cells increased by using IL-2 and IL-7. Our data showed that IL-2 and IL-7 significantly affected the generation of B cells from CD26 positive cord blood mononuclear cells. On the other hand, NK (NKp46+) derived CD26+ cells increased by IL-15 and IL-2. Conclusion: Taking all into account, we conclude that B, T, and NK cells can differentiate from the CD26+ subset of mononuclear cord blood cells by using key regulatory cytokines.
Nahid Naderi; Ali Akbar Pourfathoolah; Mahin Nikougoftar; Kamran Alimoghadam; Ardeshir Ghavamzadeh; Seyed Mohammad Moazzeni
Volume 2, Issue 1 , March 2005, , Pages 21-28
Abstract
Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity ...
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Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity of acute graft-versus-host disease after CB transplantation. Objectives: The aim of this study was the isolation of cord blood and peripheral blood dendritic cells and comparison of their functional competence and determination of their probable role in graft versus host disease after stem cell transplantation. Methods: In this study, fresh peripheral blood DCs (PBDCs) were enriched as HLA-DR + cells, lacking the CD3, CD11b, CD14, CD16, CD19 and CD56, using immunomagnetic bead depletion. For cord blood dendritic cells (CBDCs) enrichment CD34 + and CD66b+ cells were needed to be depleted too. Immunomagnetically enriched PB/CB dendritic cells were co-cultured with adult T lymphocytes and cell proliferation was measured by 3H-thymidine incorporation. Results: Results showed that CBDCs were significantly poor stimulators of the mixed leukocyte reaction as compared with PBDCs (P < 0.05). Conclusion: The demonstrated impairment of CBDCs function could be of importance in interpretation of the low incidence and milder severity of graft-versus-host disease (GVHD) in umbilical CB transplantation compared with peripheral blood or bone marrow stem cell transplantation.
Mohammad Hojjat Farasangi; Mahmood Jeddi-Tehrani; Seyed Mohsen Razavi; Ramazan Ali Sharifian; Ahmad Shamsian Khoramabadi; Hojatollah Rabbani; Fazel Shokri
Volume 5, Issue 1 , March 2008, , Pages 25-35
Abstract
Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have hetero-geneous clinical courses, thus several biological parameters need to be added to the cur-rent clinical staging systems to predict disease outcome. Recent immunophenotypic stud-ies performed mainly in Western populations ...
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Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have hetero-geneous clinical courses, thus several biological parameters need to be added to the cur-rent clinical staging systems to predict disease outcome. Recent immunophenotypic stud-ies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL. Objectives: To investigate the expression pat-tern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between in-dolent and progressive groups. Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry. Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast ma-jority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and inten-sity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) pa-tients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients. Conclusion: Our results obtained in an Asian ethnic popula-tion confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.
Ali Akbar Amirzargar; Morteza Bagheri; Ardeshir Ghavamzadeh; Kamran Alimoghadam; Farideh Khosravi; Mohammad Hossein Nicknam; Mandana Moheydin; Bita Ansaripour; Batul Moradi; Behrouz Nikbin
Volume 1, Issue 1 , June 2004, , Pages 26-33
Abstract
Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion ...
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Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion of cytokines is dependent, at least in part, on genetic polymorphism (nucleotide variations) within the promoter region or other regulatory sequences of cytokine genes. The majority of polymorphisms described are single nucleotide polymorphism (SNPs). The objective of this study was to analyze the genetic profile of Th1 and Th2 cytokines in 30 Iranian patients with CML and 40 healthy subjects. Methods: In the patients and control subjects, the allelic and genotype frequencies were determined for the cytokine genes. All typing were performed by PCR-SSP assay. Allele and genotype frequencies were calculated and compared with those of normal controls. Results: The results showed that the most frequent alleles in our patients were TGF-b TG/TG, IL-4 T at position -1089, C at position -590, T at position -33 and IL-10 A at position -1082. Whereas the following alleles - TGF-b CG/CG and IL-10 C at position -592 – were seen in much lower frequencies. Conclusion: In conclusion, it could be suggested that the frequency of high producing TGF-b alleles and low producing IL-4 and IL-10 alleles in the CML patients is higher than the normal subjects.
Mozhgan Moghtaderi; Shirin Farjadian; Sara Kashef; Soheila Alyasin; Maryam Afrasiabi; Marzieh Orooj
Volume 9, Issue 1 , March 2012, , Pages 32-38
Abstract
Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about ...
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Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. Objectives: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. Methods: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow’s milk, hen’s egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Results: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow’s milk (31%), hen’s egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Conclusion: Our results showed that cow’s milk, hen’s egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.
Seyyed Mohammad Ali Ghayumi; Kambiz Aghasadeghi; Mehrnoosh Dorouchi; Abbas Ghaderi
Volume 3, Issue 2 , June 2006, , Pages 61-65
Abstract
Background: The HER-2/neu gene is located on chromosome 17q21 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity reported to be released in soluble form in various malignancies. Objective: To evaluate the clinical significance of soluble Her-2/neu as a diagnostic marker in ...
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Background: The HER-2/neu gene is located on chromosome 17q21 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity reported to be released in soluble form in various malignancies. Objective: To evaluate the clinical significance of soluble Her-2/neu as a diagnostic marker in lung cancer. Methods: Serum levels of soluble HER-2/neu were measured in 43 patients with lung cancer and 42 age and sex matched controls by an enzyme immunoassay method. Results: Mean serum level of soluble Her-2/neu in cancer patients was 6.07±10.37 ng/ml which was significantly higher than the control group (P < 0.05). Cigarette smoking had no effect on the level of soluble HER-2/neu. A cut off value of 6.1ng/ml revealed a high specificity (95%) for diagnosis of lung cancer, but a very low sensitivity (14%). Conclusion: The results of this study show an increased level of soluble HER-2/neu in the sera of lung cancer patients with a high specificity but low sensitivity for diagnosis of lung cancers.
Maryam Roudbary; Shahla Roudbar Mohammadi; Mahmood Bozorgmehr; Seyed Mohammad Moazzeni
Volume 6, Issue 2 , June 2009, , Pages 67-74
Abstract
Back ground: Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are ...
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Back ground: Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are carbohydrates such as mannans, β glucans and chitins, and proteins that partially modulate the host immune responses. Dendritic cells (DC), as the most important antigen-presenting cells of the immune system, play a critical role in inducing immune responses against different pathogens. Objective: We investigated the effect of the cell wall protein fraction (CPF) of C. albicans on DC maturation. Methods: The CPF of C. albicans cells was extracted by a lysis buffer containing sodium dodecyl sulphate, 2-mercaptoethanol and phosphate-buffered saline. The extract was dialyzed and its protein pattern was evaluated by electrophoresis. Dendritic cells were purified from Balb/c mice spleens through a three-step method including mononuclear cell separation, as well as 2-h and overnight cultures. The purified CPF was added at different concentrations to DC. The purity and maturation status of DC were determined by flow cytometry using monoclonal antibodies against CD11c, MHC-II, CD40 and CD86. Results: Treatment of DC with 10 μg/ml of CPF increased the expression of maturation markers including MHC-II, CD86 and CD40 on DC compared to the control group. Conclusion: In this study we used C. albicans CPF with the molecular weight of 40-45 kDa for pulsing and maturation of dendritic cells. Since according to our results CPF significantly increased the expression of maturation markers on DC, we suggest that CPF may act as an efficient immunomodulator, or may be used as a potential adjuvant to boost the host immune system against infections.
Ahmad Khalili; Zuhair Muhammad Hassan; Shahram Shahabi; Ali Akbar Pourfathollah; Seyed Nasser Ostad; Shokoofe Noori; Mehdi Mahdavi; Habib Haybar; Ladan Langroudi
Volume 10, Issue 2 , June 2013, , Pages 70-82
Abstract
Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, ...
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Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. Objectives: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Methods: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. Results: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. Conclusion: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
Seyed Javad Hasheminia; Sayyed Hamid Zarkesh-Esfahani; Sepideh Tolouei; Vahid Shaygannejad; Hedaiatallah Shirzad; Morteza Hashemzadeh Chaleshtory
Volume 11, Issue 2 , June 2014, , Pages 74-83
Abstract
Background: Multiple sclerosis (MS) is a T cell mediated autoimmune disease with unknown etiology. Appropriate MS therapeutic strategies need thorough understanding of both disease etiology and pathogenesis mechanisms. Ligation of TLR-2 and TLR-4 stimulates the production of several cytokines leading ...
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Background: Multiple sclerosis (MS) is a T cell mediated autoimmune disease with unknown etiology. Appropriate MS therapeutic strategies need thorough understanding of both disease etiology and pathogenesis mechanisms. Ligation of TLR-2 and TLR-4 stimulates the production of several cytokines leading to CNS autoimmunity and neurodegenerative diseases. Objective: To find a relationship between MS disability and TLR-2 and TLR-4 expression on mononuclear cells in the blood of MS patients. Methods: Forty-five new case (NC) MS patients (33 females and 12 males) and 45 age and gender-matched healthy controls (HC) were recruited to the study. PBMCs were prepared and the expressions of TLR-2 and TLR-4 were assessed by flowcytometry technique using appropriate monoclonal antibodies. Results: Our results showed that the expression of TLR-2 and TLR-4 proteins in the patients group was significantly higher than that of healthy controls. TLR-2 but not TLR-4 was correlated with expanded disability status scale (EDSS) scores. Conclusion: High expressions of TLR-2 and TLR-4 may represent a state of innate immune activation in patients with MS.
Mohammad Mahdi Eftekharian; Amir Hassan Zamani; Seyed-Mohammad Moazzeni
Volume 7, Issue 2 , June 2010, , Pages 74-82
Abstract
Background: Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions ...
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Background: Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions such as autoimmune diseases. Objective: The aim of this study was to investigate the in vivo effects of calcitriol (active form of vitamin D3) on DCs. Methods: 0.1 microgram calcitriol was injected intra-peritoneally into C57BL/6 mice every other day within 3 weeks, and spleen DCs were extracted by magnetic beads. The phenotypic and functional properties of DCs were studied by flow cytometry and mixed lymphocyte reaction (MLR), respectively. Results: The expression of CD86 and MHC II, as maturation markers and costimulatory molecules were significantly decreased (p=0.028 and p=0.047, respectively) while CD11b expression, as a marker of mice myeloid DCs which mostly induces Th2 cytokine profile, was significantly increased (p=0.011). Allogeneic T cell stimulation in MLR was also significantly inhibited in comparison with the control groups (p<0.05). Conclusion: Our data indicate that in vivo calcitriol administration inhibits maturation and activation of DCs in the same manner as in vitro conditions.
Masumeh Gorgian Mahmoody; Taravat Bamdad; Maoud Pasania; Hoorieh Soleimanjahi; Somayeh Pouyanfard; Hamidreza Hashemi; Mohammad Asghari-Jafarabadi
Volume 8, Issue 2 , June 2011, , Pages 76-84
Abstract
Background: Studies on efficacy of various vaccines that prevent or reduce the primary and recurrent HSV-1 infection have demonstrated the importance of cellular immunity for protection against the infection. We previously used DNA vaccination to induce cellular immunity against HSV-1 infection in mice. ...
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Background: Studies on efficacy of various vaccines that prevent or reduce the primary and recurrent HSV-1 infection have demonstrated the importance of cellular immunity for protection against the infection. We previously used DNA vaccination to induce cellular immunity against HSV-1 infection in mice. Objective: The aim of our study was to evaluate the effect of LIGHT, a member of TNF super family, on the kinetic of CTL response induced by HSV-1 glycoprotein B based DNA vaccine. Methods: Using a granzyme B ELISA for detection and analysis of CD8+ T cells, CTL activity was determined in the spleen of BALB/c mice at various time points after primary and booster dose of vaccination. The kinetics of CTL response to primary and secondary HSV-1 infection and DNA vaccination were compared to those induced by DNA vaccination in combination with LIGHT adjuvant in the present study. Results: In primary and secondary immunization, the CTL activity in the HSV injected group peaked 7 days and 12 hours post immunization, respectively. After 5 days, LIGHT could neither accelerate the CTL response compared to DNA vaccination alone nor could enhance the CTL activity in the primary and the first peak of memory response, the amount of granzyme B induced by the LIGHT containing vaccine was significantly higher than that induced by the vaccine without the adjuvant. Conclusion: Although LIGHT enhances the cellular response in the booster dose of vaccination, it does not accelerate the CTL response.
Mahmoud Orazizadeh; Donald M Salter
Volume 2, Issue 2 , June 2005, , Pages 78-86
Abstract
Background: Previous studies have shown that Galectin-3, a member of lectin family, is expressed in developing cartilage in mouse embryo and also in growth plate of long bones. Objective: In the present work, the expression pattern of Galectin-3 in normal and various grades of osteoarthritic (OA) ...
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Background: Previous studies have shown that Galectin-3, a member of lectin family, is expressed in developing cartilage in mouse embryo and also in growth plate of long bones. Objective: In the present work, the expression pattern of Galectin-3 in normal and various grades of osteoarthritic (OA) human articular cartilage has been studied. Methods: Using immunohistochemistry and standard western blotting, the in vivo and in vitro expression pattern of Galectin-3 in normal and OA human articular cartilage were assessed. Results: Immunohistochemical studies showed a similar pattern of Galectin-3 expression in normal and mild OA but severe OA showed different strong expression in all zones of human articular cartilage. Conclusion: Increased expression pattern of Galectin-3 in advanced stages of OA may occur as a result of the imbalance of chondrocyte homeostasis that occurs in OA cartilage and provides a condition to modify normal chondrocyte to an OA chondroctye.
Abdolkarim Sheikhi; Hossein B. Ganji; Razieh Sheikhi
Volume 4, Issue 2 , June 2007, , Pages 79-84
Abstract
Background: Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their re-cruitment and activation is incompletely ...
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Background: Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their re-cruitment and activation is incompletely understood. The major subpopulation of uNK cells in humans expresses CD56, the neural cell adhesion molecule (NCAM)-1 while their counterpart in mouse expresses asialoGM1, a brain ganglioside. Sympathetic nerves ex-press NCAM-1 which mediates homotypic binding. Sympathetic fibers innervate the me-sometrial vasculature but their relationship to the myometrial and decidual uNK cell re-cruitment is unknown. Objective: The present study aims to explore positional relation-ship between natural killer cells and distribution of nerves in decidualized mouse uterus. Methods: Immunohistochemistry and mRNA expression for the enzyme tyrosine hy-droxylase were used to map sympathetic nerve fibre distribution within C57BL/6 implan-tation sites and to address a relationship with uNK cells. Results: Tyrosine hydroxylase positive neurons were identified in the mesometrium closely associated with uterine arter-ies. Staining became gradually vanished as the nerves crossed the myometrium and en-tered the decidualized uterus. No neuronal stain was associated with the spiral arteries. Periodic Acid Schiff’s reactive uNK cells were absent from the mesentery, but abundant in decidua basalis where they are associated with non-innervated vessels. Conclusion: Data suggest that the recruitment of uNK progenitor cells to the uterus is unlikely to be dependent on signaling by the sympathetic nervous system
Zahra Meshkat; Hoorieh Soleimajjahi; Mahmoud Mahmoudi; Zuhair Mohammad Hassan; Hessam Mirshahabi; Mojtaba Meshkat; Maryam Kheirandish
Abstract
Background: Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among female population worldwide. Specific human papillomaviruses and, most notably, HPV types 16 and 18 are recognized as being caus-ally associated with cervical carcinomas. The early ...
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Background: Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among female population worldwide. Specific human papillomaviruses and, most notably, HPV types 16 and 18 are recognized as being caus-ally associated with cervical carcinomas. The early HPV type 16 genes, E6 and E7, di-rectly participate in the in vitro transformation of primary human keratinocytes and rep-resent an excellent target for immune therapy of HPV related disease. Objective: The aim of this study was the evaluation of the efficacy of a DNA vaccine containing human papillomaviruse type 16 E7 gene (Iranian isolate) in induction of CTL responses in an animal model. Methods: In this study, the expression vector containing HPV type 16 E7 gene was constructed and chosen as a model antigen in the development of a thera-peutic DNA vaccine in an animal model. CTL responses, cytokine assay, lymphocyte stimulation test, CD4 and CD8 staining and flowcytometry were done for evaluating of the immune responses. Results: Our findings indicate that the target DNA vaccine can induce an E7-specific CTL response, which is important in the lysis of infected tumor cells, compared to negative control (p<0.005) after in vivo immunization in the mouse system. Conclusion: The developed vaccine may be promising as an anti-cancer vac-cine.
Fatemeh Roodbari; Farzaneh Sabahi; Mohamad Nabi Sarbolouki; Farzaneh Barkhordari; Ahmad Adeli; Amel Jamedar; Fereidoun Mahboudi
Volume 9, Issue 2 , June 2012, , Pages 86-97
Abstract
Background: Development of an effective vaccine is highly needed in order to restrict the AIDS pandemic. DNA vaccines initiate both arms of immunity without the potential of causing disease. HIV-1 p24 and gp41 (gag and env) proteins play important roles in viral pathogenesis and are effective candidates ...
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Background: Development of an effective vaccine is highly needed in order to restrict the AIDS pandemic. DNA vaccines initiate both arms of immunity without the potential of causing disease. HIV-1 p24 and gp41 (gag and env) proteins play important roles in viral pathogenesis and are effective candidates for immune induction and vaccine design. Objective: In this study, new DNA vaccine candidates constructed from HIV-1 fused p24- gp41 or gp41 alone were evaluated in Balb/c mice for induction of cellular and humoral immune responses. Methods: Recombinant plasmids, pcDNA3.1/Hygro expression vector containing immunogenic sequences of fused p24-gp41 or gp41alone were produced. Dendrosome used as a system for carrying vectors in laboratory animals, and an IL-12 containing vector (pCAGGS-IL-12) was co-immunized with the p24-gp41 vector as a genetic adjuvant. Induction of effective immune responses against the designed vectors as DNA vaccine candidates in Balb/c mice was evaluated. Levels of total antibodies, IgG isotypes (IgG2a and IgG1); IFN-γ and IL-4 were measured by ELISA. MTT assay was used to evaluate lymphoproliferation. Results: The results confirmed that the immunogenic epitopes of both p24 and gp41 genes are highly effective inducers of immune responses, and administration of fused p24-gp41 alone or along with IL-12 resulted in further enhancement of immune responses. Group 4 that received fused fragments (p24-gp41) along with an IL-12 expressing vector demonstrated a significantly higher Stimulation Index (SI) and IFN- production (p<0.0001) with a significant increase in IgG2a/IgG1 ratio, indicating the stimulation of CMI towards Th1. Although gp41 containing vector (group 6) also showed significant increases in both proliferation and IFN- production, the responses were persistently lower than that of p24-gp41 containing vectors. Total antibody production was highest in group 6 as expected. Conclusion: Dendrosome proved to be an efficient carrier of recombinant plasmids constructed in this study. Further studies are necessary to evaluate these constructs as HIV vaccine candidates.
Yongan Liu; Wei Nie; Yu Jin; Anshan Zhuo; Yuansheng Zang; Qingyu Xiu
Volume 13, Issue 2 , June 2016, , Pages 89-99
Abstract
Background: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. Objective: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. Methods: ...
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Background: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. Objective: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. Methods: Firefly luciferase reporter plasmids pEZX-MT01-wild-type-BTLA and pEZX-MT01-mutant-BTLA were constructed. Lymphocytes were nucleofected with miR-155 inhibitor or negative control (NC). Then, naïve CD4+ CD62L+ helper T cells purified from lymphocytes were stimulated with immobilized antibody to CD3 and soluble antibody to CD28. miR-155 and BTLA expression were examined by real-time RT-PCR. Cell surface CD69 expression and IL-2 secretion were measured by ELISA and flowcytometry, respectively. Results: Luciferase reporter assay showed that miR-155 targeted the BTLA 3’UTR region. Compared with non-stimulated condition, both miR-155 and BTLA mRNA expression were upregulated after T cell activation. Similar results were observed for BLTA protein expression. Compared with NC, the miR-155 inhibitor decreased miR-155 by about 45%, but did not influence BTLA mRNA expression. Compared with NC, the miR-155 inhibitor decreased the surface BTLA expression by about 60%. Upregulation of BTLA in miR-155 knockdown CD4+ T cells did not influence the cell surface expression of CD69, an early activation marker (p=0.523). Similarly, IL-2 production was not changed. Conclusion: miR-155 is involved in the inhibition of BTLA during CD4+ T cell activation. These results might serve as a basis for an eventual therapeutic manipulation of this pathway to treat inflammatory and autoimmune diseases.