Original Article
Noha Mohamed El Husseiny; Walaa Abd El Fattah Attya Elkak; Mervat Said El Ansary; Engy Mohamed Abd El Aziz El Khateeb; Mervat Wagih Mattar; Doaa Mohamed El Demerdash
Volume 14, Issue 1 , March 2017, Pages 1-12
Abstract
Background: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and ...
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Background: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. Objective: To compare effects of traditional cytokine cocktail (TNF-α + IL-1β) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC. Methods: The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation; Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects; Group 3: MPLA group which included 10 AML subjects. Results: TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful. Conclusion: The effect of MPLA in DC maturation is comparable with traditional DC maturation cocktail.
Original Article
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.
Original Article
Morteza Hosseinzadeh; Mohsen Nafar; Pedram Ahmadpoor; Farshid Noorbakhsh; Mir Saeed Yekaninejad; Mohammad Hossein Niknam; Aliakbar Amirzargar
Volume 14, Issue 1 , March 2017, Pages 24-34
Abstract
Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells ...
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Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells (PBMCs) can predict the clinical outcome of kidney allografts. Methods: We obtained blood samples from 52 renal transplant patients before transplant, and 2, 90, and 180 days post-transplantation in order to analyze the surface expressions of TLR-2 and TLR-4 on peripheral blood monocytes. The expression patterns of TLR-2 and TLR-4 were compared between patients with graft dysfunction (GD) and those with well-functioning graft (WFG). Results: Significantly different mean dynamic changes in surface expression of TLR-2, according to percentage of TLR-2+ cells, between (the GD and WFG) groups existed at most time-points before and after renal transplantation (p=0.007) with the exception of day 2 post-transplantation. We observed significantly higher mean fluorescence intensities of TLR-2 and TLR-4 on CD14+ cells in the GD group compared to the WFG group. This finding was particularly observed 180 days post-transplantation (p=0.001). Based on TLR-2 and TLR-4 protein expression for each step, multiple logistic regression and ROC curve analysis revealed that an increase in CD14+ TLR-2+ monocytes within the 90 days post-transplantaton was associated with increased risk of GD at 180 and 365 days post-transplantation [odds ratio (OR)=1.27, p=0.005)]. Conclusion: Sequential monitoring of TLR-2 and TLR-4 expression patterns in peripheral blood monocytes appear to be prognostic and predictive biomarkers for early and late kidney allograft outcomes.
Original Article
Naceur Mejri; Imed Eddine Hassen; Jenny Knapp; Mouldi Saidi
Volume 14, Issue 1 , March 2017, Pages 35-50
Abstract
Background: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach. Objective: ...
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Background: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach. Objective: To elucidate immunosuppressive effects of bioactive factors contained in chromatographic fractions from hydatid cystic fluid (HCF) of Echinococcus granulosus. Methods: Hydatid cystic fluid was fractionated by reverse phase chromatography. Non-specific Concanavalin A-driven proliferation of spleen cells was used to determine specific inhibitory fractions. Trypan blue exclusion test and flowcytometry analysis were performed to check whether highly inhibitory fractions of HCF have apoptotic effect on peritoneal macrophages. Western blot analysis was used to determine proteolytic effects of parasitic antigens on major histocompatibility complex (MHC) class II (I-a) contained in membrane proteins extract from macrophages. Results: High concentrations of HCF and few of chromatographic fractions suppressed spleen cells proliferation. Fractions 7 and 35 were the highest inhibitory fractions. Specifically fraction 35 and to a lesser extent HCF induced apoptosis in peritoneal naive macrophages. However, HCF and the fraction 7 proteolytically altered the expression of MHC class II molecules on peritoneal macrophages. The proteolytic molecule was identified to be a serine protease. Macrophages taken at the chronic and end phase from cystic echinococcosis-infected mice were able to uptake and process C-Ovalbumine-FITC. These cells expressed a drastically reduced level of (I-a) molecules. Conclusion: Our study present new aspects of immune suppression function of E. granulosus. Further molecular characterization of apoptotic and proteolytic factors might be useful to develop immunotherapeutic procedure to break down their inhibitory effects.
Original Article
Vamsi Lavu; Vettriselvi Venkatesan; Priyanka Venugopal; Bhaskar Venkata Kameswara Subrahmanya Lakkakula; Solomon Franklin Durairaj Paul; Kumarasamy Peria; Suresh Ranga Rao
Volume 14, Issue 1 , March 2017, Pages 51-58
Abstract
Background: Cytokines are suggested to play a role in periodontitis. Objective: To determine and compare the levels of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) samples amongst healthy individuals and those with chronic periodontitis. ...
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Background: Cytokines are suggested to play a role in periodontitis. Objective: To determine and compare the levels of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) samples amongst healthy individuals and those with chronic periodontitis. Further to compare the GCF cytokine levels in three genotype classes defined by the respective gene polymorphisms. Methods: The study was conducted on 41 chronic periodontitis patients and 40 healthy volunteers. IL-1β and TNF-α were quantified in GCF by cytometric bead array. DNA was extracted from peripheral blood samples and genotyping of IL1B +3954C/T (rs1143634) IL1B -511G/A (rs16944), TNFA -1031T/C (rs1799964) and TNFA -863C/A (rs1800630) polymorphisms were performed using Sanger sequencing and Taqman SNP genotyping assays methods. Results: Both IL-1β and TNF-α levels were significantly higher in chronic periodontitis group compared to the controls. IL-1β and TNF-α levels did not significantly differ in genotype classes of the respective polymorphism (IL1B -511G/A, TNFA -1031T/C and TNFA -863C/A). However, individuals with CT genotype of IL1B +3954C/T showed higher levels of IL-1β in the gingival crevicular fluid (ANOVA p<0.05). Conclusion: The results of this study revealed the presence of higher levels of IL-1β and TNF-α in subjects with periodontitis and genetic control of IL-1β levels in our samples of Indians.
Original Article
Mohammadrasul Zareinejad; Afshin Samiei; Behnaz Valibeigi; Tahereh Gholami; Soheila Zareifar; Zahra Amirghofran
Volume 14, Issue 1 , March 2017, Pages 59-72
Abstract
Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants ...
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Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants were studied in 164 ALL patients and compared to 175 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The relationship between these variants and clinical and laboratory features of the patients and response to therapy were evaluated. Results: No significant differences in genotype and allele frequencies existed between patients and controls. The rs1884444TG genotype was significantly lower in patients who relapsed (24.2%) compared to those without relapse (55.9%, p=0.006). Fewer patients who relapsed had evidence of the G allele (P=0.034). The TG genotype was associated with a longer complete remission at1804±116 days compared to other genotypes (<1217 days, p=0.028), however this result was not significant in multivariate analysis. The rs10889677 AA genotype and A allele was associated with age (p<0.041) and platelet number (p=0.03) in precursor-B cell ALL (B-ALL) patients. Both occurred more frequently in patients aged 2-10 years (63.6% and 66%, respectively) and in those with platelets >100×103μL (68.4% and 52.4%, respectively). Conclusion: Our findings showed a lack of association of the studied polymorphisms with the risk of ALL. The influence of the rs1884444 polymorphism on relapse rate and association of rs10889677 AA genotype with favorable prognostic factors suggest the influence of the studied polymorphisms on ALL response to therapy and prognosis.
Original Article
Soheila Alyasin; Reza Amin; Ali Fazel; Mohammad Hossein Karimi; Seyed Hesamedin Nabavizadeh; Hossein Esmaeilzadeh; Maryam Babaei
Volume 14, Issue 1 , March 2017, Pages 73-80
Abstract
Background: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 ...
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Background: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 (IL-23) in the pathogenesis of adultallergic asthma has been studied. Objective: To explore IL-23 serum levels and its expression in persistent asthma compared with healthy children younger than five years old. Method: Blood samples of 40 children with mild and severe persistent asthma were compared to 34 healthy children regarding IL-23 serum levels and gene expression using enzyme-linked immunosorbentassay (ELISA) and real time quantitative polymerase chain reaction (PCR). Results: The IL-23 gene expression level was significantly different in the 25 children with mild persistent asthma and the 15 children with severe persistent asthma compared to the control group (p=0.001).There was no significant difference in IL-23 gene expression level between the two groups of patients with mild and severe persistent asthma. A significant difference was seen in IL-23 serum levels between the 25 children with persistent asthma and control group (p=0.002).Conclusion: For pre-school children with history and physical exam in favor of asthma which cannot be tested by spirometry, IL-23 serum levels may be an auxiliary biomarker for the diagnosis of asthma.
Original Article
Hossein Esmaeilzadeh; Elmira Esmaeilzadeh; Mohammad Faramarzi; Mohammad Nabavi; Mohammad Farhadi
Volume 14, Issue 1 , March 2017, Pages 81-88
Abstract
Background: A clear association between allergy and nasal polyposis (NP) is not
determined and the role of food intolerance in patients with NP is not investigated by
oral food challenge (OFC). Objective: To investigate the relation of salicylate food
intolerance and atopy in patients with NP according ...
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Background: A clear association between allergy and nasal polyposis (NP) is not
determined and the role of food intolerance in patients with NP is not investigated by
oral food challenge (OFC). Objective: To investigate the relation of salicylate food
intolerance and atopy in patients with NP according to recurrence and aspirin
sensitivity. Methods: A cross sectional multicenter study was done in two tertiary
centers for allergy in Iran. Adult patients with NP were selected for the study that had
been referred to allergy clinics. The oral aspirin challenge (OAC) test was performed to
identify aspirin exacerbated respiratory disease (AERD) and the OFC test was used to
investigate food intolerance. Atopic evaluation was performed by skin-prick tests, nasal
smear and blood eosinophil count as well as serum total IgE. Results: One hundred and
nineteen Iranian patients (female to male ratio 1.05) with NP were enrolled (mean age,
38 ± 11 years). Recurrence of nasal polyposis was 64.7%. OAC was performed in all
cases; 43.79% cases had aspirin hypersensitivity. In addition, OFC tests determined that
69.9% of patients had salicylate food allergy. Salicylate food intolerance was
significantly higher in NP cases with AERD than in aspirin tolerant patients (p<0.05).
Yet, positive skin prick test was not associated with NP recurrence and AERD.
Conclusion: Atopy and NSAID exacerbated respiratory disease; therefore, they can
both be considered as predictors of NP recurrence. Our study also showed that salicylate
food intolerance was associated with AERD in nasal polyposis.
Volume 14, Issue 1 , March 2017, Pages 89-89
