Romina Kazemi; Mobin Mohammadi; Samira Salimiyan; Sara Aliakbari; Moslem Ahmadi; Mohammad Reza Rahmani
Abstract
Background: Low-dose naltrexone (LDN) is involved in the treatment of inflammatory and immune system diseases and can affect immune cells. Mesenchymal stem cells (MSCs) are known for their immunomodulatory effects and the potential for the treatment of certain types of autoimmune diseases.Objective: ...
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Background: Low-dose naltrexone (LDN) is involved in the treatment of inflammatory and immune system diseases and can affect immune cells. Mesenchymal stem cells (MSCs) are known for their immunomodulatory effects and the potential for the treatment of certain types of autoimmune diseases.Objective: To investigate the long-term effects of LDN on human adipose-derived mesenchymal stem cells (ASCs) to see how their immunomodulatory properties are affected and also how LDN-treated ASCs interact with other immune cells present in peripheral blood mononuclear cells (PBMCs).Methods: After 14 days of treatment, the ability of LDN-treated ASCs to modulate PBMC proliferation in a two-way mixed lymphocyte reaction (MLR) model was assessed using XTT. The relative expression of IDO, PD-L1, COX-2, HGF genes, and the level of IL-6 and TGF-β cytokines were measured in IFN-γ stimulated and unstimulated ASCs (treated and not treated cells) using real-time PCR and ELISA respectively.Results: Unstimulated ASCs treated with 10-8 M Naltrexone (10-8 M NTX) showed higher levels of TGF-β, compared with the controls (P<0.05). Stimulated ASCs treated with 10-6 M NTX showed elevated expression of IDO, PD-L1 genes, and IL-6 level (P<0.05).Conclusion: Our results demonstrated that various LDN concentrations have dissimilar effects on ASCs’ immunomodulatory properties. A higher LDN concentration induced an alteration in the immunomodulatory features of ASCs.
Hao Zheng; Qiaozhen Kang; Chenglong Zhang; Lu Yang; Xin Liu
Abstract
Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR ...
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Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR agonist.Objective: To explore the effect of the rMBP-NAP on the OXA-induced AD in a mouse model and clarify the possible action mechanism.Methods: The AD animal model was induced by repeated administration of oxazolone (OXA) in BALB/c mice. H&E staining was used to analyze the ear epidermis thickness and the number of infiltrating inflammatory cells. TB staining was used to detect mast cell infiltration in the ear tissue. ELISA was used to analyze the secretion of cytokines IL-4 and IFN-γ in peripheral blood. qRT-PCR was used to determine the expression levels of IL-4, IFN-γ, and IL-13 in ear tissue.Results: OXA induced the establishment of an AD model. After the rMBP-NAP treatment, the thickness of the ear tissue and the number of mast cells infiltrated in AD mice reduced, and the serum and ear tissue levels of IL-4 and IFN-γ increased, but the ratio of IFN-γ (rMBP-NAP group)/IL-4 (rMBP-NAP group) was greater than the ratio of IFN-γ (sensitized group)/IL-4 (sensitized group).Conclusion: The rMBP-NAP improved the disease symptoms including skin lesions in AD, alleviated the inflammation in ear tissue, and restored the Th1/2 balance by inducing a shift from the Th2 to the Th1 response. The results of our work support the use of rMBP-NAP as an immunomodulator for AD treatment in future investigations.
Bilal Mahmood Beg; Aqeel Javeed; Muhammad Ashraf; Arfan Ahmad; Adeel Sattar; Mehmood Ahmad
Abstract
Background: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. Objective: This study aimed to evaluate the impact of niclosamide on immune response of mice. Methods: Niclosamide was administered ...
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Background: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. Objective: This study aimed to evaluate the impact of niclosamide on immune response of mice. Methods: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages. Results: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-β1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner. Conclusion: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-β1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.
Elisa Vintiñi; Marcela Medina
Volume 14, Issue 4 , December 2017, , Pages 325-339
Abstract
Background: Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic in vivo and in vitro infection induced by some viruses. Objective: To determine whether non-viable Lactobacillus casei CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture ...
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Background: Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic in vivo and in vitro infection induced by some viruses. Objective: To determine whether non-viable Lactobacillus casei CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture models of peripheral blood mononuclear cells (PBMC) and A549 cells. Methods: T and NK cell activation was evaluated by flow cytometry and levels of TNF-α, IFN-γ, IL-10, IL-29, and IL-17 by ELISA. Cells in direct contact with A549 (PBMC-A549) and cells with no contact with it (PBMC//A549) were used for this purpose. PBMCs alone and both co-culture systems were stimulated for 24 h with the following stimuli: LPS (10 µg/ml), LcM (106 UFC/ml), Poly I:C (2 µg/ml), Poly I:C+LcM, and LcM (3 h)+Poly I:C. Moreover, unstimulated cells were used as a control. Results: Poly I:C and LcM (3 h)+Poly I:C in PBMC-A549 showed a significant increase in the percentage of CD8+ expression (p<0.05). All stimuli induced significant activation from T CD4+, CD8+ cells compared with unstimulated PBMCs in both co-culture cells system. However, activation percentages were higher in direct co-culture. Poly I:C induced a higher level of pro-inflammatory TNF-α and IFN-γ cytokines as well as IL-17 and IL-29 with lower IL-10 levels in both co-culture systems while LcM induced a beneficial pattern of cytokines that would regulate Poly I:C effect. Conclusion: This in vitro model allowed us to highlight the potential of LcM as a modulator of anti-viral immune response and suggest its potential use in formulations against RNA respiratory viruses.
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.
Murat Karamese; Hakan Aydin; Emin Sengul; Volkan Gelen; Cigdem Sevim; Duran Ustek; Emre Karakus
Volume 13, Issue 3 , September 2016, , Pages 220-228
Abstract
Background: Probiotics are “live”, beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. Objective: To investigate the immunomodulatory effects of a probiotic mixture, ...
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Background: Probiotics are “live”, beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. Objective: To investigate the immunomodulatory effects of a probiotic mixture, including Lactobacillus and Bifidobacterium species, by detecting serum cytokine and immunoglobulin levels. Methods: The rats were randomly divided into 4 groups. The first group was “Control group” and other 3 groups were probiotic application groups who received different doses of probiotics. The probiotic mixture included 12 probiotic bacteria, mostly Lactobacillus and Bifidobacterium strains. Probiotic mixture was administered to rats for 12 consecutive days. TNF-α, TGF-β, IL-1-β, IL-6, and IL-10 levels as well as serum IgG and IgA concentrations were detected in the sera after 12 days. Results: Probiotics led to a decrease in the levels of TNF-α, IL-6 and TGF-β; however, they led to increase in the serum levels of IL-10, IgG and IgA. There were significant differences between control group and probiotic application groups (p<0.05). Conclusion: These data suggest that the commensal microbiota are important for stimulating both proinflammatory and regulatory responses in order to rapidly clear infections and minimize inflammation-associated tissue damage.
Ladan Sadeghi; Eskandar Kamali-Sarvestani; Negar Azarpira; Mehrdad Shariati; Mohammad Hossein Karimi
Volume 11, Issue 3 , September 2014, , Pages 177-188
Abstract
Background: Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity. Objective: To evaluate the immunomodulatory ...
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Background: Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity. Objective: To evaluate the immunomodulatory effects of MSCs supernatant on maturation and function of DCs. Methods: Bone marrow derived mice MSCs were isolated and cultured. Twenty-four, forty-eight and seventy-two hours after passage 6, supernatants were collected and MSCs were assessed by cytometric analysis for the expression of CD34, CD44, CD45 and SCA-1. Splenic DCs were isolated using MACS and then co-cultured with MSCs supernatant. Expression of CD86, CD40 and MHC-II on DCs were also evaluated by cytometry. H 3-thymidine incorporation by proliferating T cells was determined in two separate MLR assay settings. In one setting, DCs were co-cultured with T cells in the presence of MSCs supernatant, and in the other setting DCs were treated with MSCs supernatant and then were co-cultured with T cells. Production of IL-12, IL-6 and IL-10 cytokines was measured in the supernatant of DCs treated with MSCs supernatant. We also measured IFN- γ and IL-4 levels in MLR supernatant. Results: The results showed that 72h MSCs supernatant could decrease the expression of MHC-II and CD86. The T cell proliferation was inhibited in the presence of MSCs supernatant and MSCs supernatant treated DCs as demonstrated by MLR assay. A significant increase in IL-4 level and a non significant decrease in IFN- γ level in MLR supernatant were observed. However, IL-6, IL-10 and IL-12 production did not change significantly. Conclusion: MSCs supernatant has a time dependent effect on the maturation of DCs. Also, it could alter cytokine production from responding T cells toward Th2. Generally, the findings of this study supported the immunomodulatory effect of MSCs supernatant on DCs maturation and function.
Anita Tilwari; Narmada Prasad Shukla; Uma Devi Pathirissery
Volume 8, Issue 2 , June 2011, , Pages 96-103
Abstract
Background: Various compounds of plant origin have been widely investigated since ancient times for their possible immunomodulatory properties as well as for the treatment of a wide range of diseases. Objective: To study the immunomodulatory functions of the aqueous extract of the seeds of Abrus precatorius ...
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Background: Various compounds of plant origin have been widely investigated since ancient times for their possible immunomodulatory properties as well as for the treatment of a wide range of diseases. Objective: To study the immunomodulatory functions of the aqueous extract of the seeds of Abrus precatorius commonly known as Indian liquorice (Fabaceae), a medicinal plant native to central India. Methods: Swiss albino mice were intraperitoneally treated with three doses (0.75, 1.25 and 2.5 μg/kg b.w.) of extract for 7 days. Relative organ weight, delayed type hypersensitivity (DTH) response, haemagglutination titre (HT) and Phagocytic index (PI) were studied in various groups of animals. Results: The results showed no significant difference in relative organ weight of spleen, liver, thymus and kidney in various groups of animals. Treatment of rats with increasing concentrations of the extract decreased the footpad thickness indicating a dose related inhibitory effect of the extract on delayed type hypersensitivity. In the HT test, the plant extract showed a suppressive effect at all doses, and these changes were significant as the dose increased. Phagocytic index was also increased in a dose dependent manner. Conclusion: The reduction of antibody titre, delayed type hypersensitivity response and the increase in phagocytic index indicates that Abrus precatorius has an inhibitory effect on the immune functions in mice.
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.
Zahra Amirghofran; Abbas Azadmehr; Katayoun Javidnia
Volume 4, Issue 1 , March 2007, , Pages 26-31
Abstract
Background: Plant extracts have been widely investigated for possible immunomodu-latory properties. Objective: To study the immunomodulatory functions of the metha-nol extract of Haussknechtia elymatica (Apioideae), an herb native to south-western Iran. Methods: Delayed type hypersensitivity (DTH) skin ...
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Background: Plant extracts have been widely investigated for possible immunomodu-latory properties. Objective: To study the immunomodulatory functions of the metha-nol extract of Haussknechtia elymatica (Apioideae), an herb native to south-western Iran. Methods: Delayed type hypersensitivity (DTH) skin test and measurement of an-tibody titer after immunization with Sheep-RBC was performed. [3H]-thymidine incor-poration assay on the human lymphocytes stimulated with PHA and determination of IL-2 production using ELISA method was carried out. Results: Treatment of mice with increasing concentrations of the extract decreased the footpad thickness indicating a dose-related inhibitory effect of H. elymatica on delayed hypersensitivity. The mean antibody titers for all concentrations of the extract at primary and secondary responses were significantly less than the control. Addition of the extract to the culture of human peripheral blood lymphocytes in the presence of mitogen decreased cell proliferation dose-dependently. A dose related decrease in production of IL-2 in extract-treated cells was also observed. Conclusion: The decline of antibody titer and DTH response indi-cates that H. elymatica, by acting on the lymphocyte proliferation and IL-2 secretion, inhibits both humoral and cell-mediated immune responses.
