ImmunoRegulation
Year:2019 | Volume:2 | Issue:1|Papers Count:8

today, only a few diseases have remained that their pathology is not somehow affected by dysregulation in immune responses. Extensive literature review reveals that footprints of dysregulation in the immune response are seen in nearly all diseases, including autoimmune diseases, allergies, infections, cancers, even pulmonary, cardiovascular, dermal, ocular, otorhinolaryngological, and gynecological diseases as well as psychological disorders....

Extracellular Vesicles, including exosomes, are small membrane fragments released from many cell types, like Mesenchymal Stem Cells (MSCs). They were recognized as a mechanism of intercellular communication. They can transfer proteins, lipids and nucleic acids to other cells. Thus, they have many physiological (angiogenesis, coagulation and tissue repair, etc. ) and pathological (e. g. in autoimmune diseases and cancer) effects. The immunomodulatory properties of them have drawn a lot of interest. In particular, MSC-derived exosomes seem to have therapeutic potentials for many diseases. We reviewed the biopathological effects of exosomes and their roles in modulating immune responses.

Background: Numerous studies have been conducted on humans, animals, and cell cultures exposed to Sulfur Mustard (SM). However, the precise mechanism and cause or long-term pattern of SM injuries are not well defined. There is no protocol available for treating people with severe eye, lung, and skin ailments. The current study aimed to develop an animal model of the acute and delayed complications of SM exposure. Materials and Methods: Two strains of mice (BALB/c and C57BL/6), 6-8 weeks old at the onset of the study, were exposed to 2-Chloroethyl Ethyl Sulfide (CEES) (1-200 mg/kg) and solvents (Tyrode’ s solution, Polyethylene Glycol 300, herbal oil) for a duration of 12 hours to 7 months. The administration route was Intraperitoneal (IP) injection. The mortality rate, signs, and apparent side effects were explored. At the end of the study, the mice’ s lung, liver, and spleen tissues were extracted and fixed for future histopathological assessments. Results: Tyrode’ s solution and Polyethylene Glycol 300 solvents were not appropriate for the present research. Pathological features observed in BALB/c mice were better than the C57BL/6 mice. Overall, 10 mg/kg CEES was the most suitable dose, because it had the least mortality rate and demonstrated the most pathological findings, such as the infiltration of inflammatory cells and proliferation of fibroblasts and fibrotic tissue in the lung. Five months after the CEES administration, the delayed phase complications were studied. Conclusion: The IP injection of 10 mg/kg CEES to BALB/c mice imitates short-and long-term complications of SM exposure in humans. This model is useful for preventing and treating SM exposure.

Background: Immune cells perform unique functions against infections and imbalances in immunity associated with various diseases. Applying natural products may control immune responses. Among herbals, much attention has been paid to the immunoregulatory functions of Allium sativum. However, the effects of other Allium species on the immune system have remained undiscovered. Therefore, the current study investigated the effects of A. sativum, A. Iranicum, A. elburzense, and A. asarense bulb extracts on macrophage and lymphocyte viability. Materials and Methods: The different concentrations of aqueous extracts of the aged bulb samples were prepared and used for the incubation of examined immune cells. Macrophages and lymphocytes were isolated and cultured in the presence of different concentrations of bulb extracts of Allium species. Macrophages and lymphocytes viability was followed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: The applied Allium species had stimulatory or inhibitory effects on the examined immune cells at different concentrations. Allium sativum demonstrated the highest effects on macrophage viability indices at 1 mg/mL. The similar effects were found for A. Iranicum extract on macrophage viability indices at 0. 01 mg/mL. The bulb extract of A. sativum at the most used concentrations stimulated lymphocyte viability indices. The bulb extracts of all 4 Allium species inhibited viability indices of lymphocytes at 1 mg/mL. The bulb extracts of A. elburzense, at all of the applied concentrations, slightly affected viability indices of the macrophage and lymphocyte. Conclusion: Besides A. sativum, wild growing Allium species could be introduced to study their immunomodulatory effects on various diseases.

Background: Tumor microenvironment is an active factor participating in immunoregulation, thereby preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia as a major characteristic of solid tumors causes the expression of Hypoxia-Inducible Factor-1α (HIF-1α ). This is a transcription factor that mediates hypoxic responses of tumor cells and involves in the expression of tumor immunosuppression-related genes. Materials and Methods: In this study, we used a mouse 4T1 breast cancer model. Results: Our obtained data revealed that in vivo administration of PX-478, an inhibitor of oxygen sensitive HIF-1α , reduced the expression of Forkhead box P3 (Foxp3) transcript, a molecule that is directly controlled by HIF-1. The level of vascular endothelial growth factor, another gene controlled by HIF-1, remained unchanged. The observed results were in correlation with delayed tumor growth in tumor-bearing mice. Conclusion: Our findings indicate that the reduction in Foxp3 expression through HIF-1α inhibition using PX-478 may contribute to tumor regression.

Background: The immunologic profile of chronic urticaria is not only important for diagnostic purposes, but also for therapeutic approaches. This study evaluated the serum levels of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α ) and Interferon-ϒ (IFN-ϒ ) in patients with chronic urticaria to find a biomarker. Materials and Methods: Forty-one patients with chronic urticaria referring to the Allergy Outpatient Clinic of Rasoul Akram Hospital and 20 healthy control subjects were enrolled in the study. A questionnaire was filled and the disease activity score was determined in a one-week period for every patient. All patients underwent basic laboratory tests in addition to the Autologous Serum Skin Test. Their serum IL-6, TNF-α , and IFN-ϒ levels were also evaluated. Results: The patients were divided into two groups comprising of 20 and 21 participants according to the results of Autologous Serum Skin Tests. The serum IL-6 levels were elevated in the patients’ group (P=0. 015). However, there was no significant difference between the patients with chronic urticaria and healthy controls in the serum levels of TNF-α (P=0. 25), and IFN-ϒ (P=0. 55), neither in the exact state nor by the Mann-Whitney U test. Conclusion: Serum IL-6 level was elevated in patients with chronic urticaria, but the serum levels of IFN-ϒ and TNF-α were not significantly elevated.

Background: Polycystic Ovarian Syndrome (PCOS) is a pro-inflammatory condition that supports the development of metabolic aberration and ovarian dysfunction. Chronic inflammation and the increased levels of androgens in this group of patients and their impact on the immune system may increase the risk of developing malignancies, including ovarian cancer. Thus, we interacted ovarian tumor cells with Peripheral Blood Mononuclear Cells (PBMC) to evaluate some of their responses to the tumor microenvironment. Materials and Methods: PBMC were collected from 25 patients with PCOS and 25 healthy women and isolated by Ficoll density gradient centrifugation. Then, we measured cell proliferation and Tumor Necrosis Factor-alpha (TNF-α ) concentration at different time intervals (48 and 72 hours) after cocultivation of ovarian tumor cell lines (SKOV3, A2780) with PBMC in an indirect contact transwell system. Results: The proliferative response of executive cells during stimulation with tumor cell lines demonstrated no statistically significant difference between the patients and healthy groups, despite lower mean score in the control group. The proliferation rate after 72 h was significantly higher than that of the 48-h interval (P<0. 01). The production of TNF-α in the co-culture of the A2780 cell line significantly increased in the patients at different time intervals compared to the controls (P<0. 05). Conclusion: We observed an increased proliferative response of effector cells and TNF-α production in PCOS patients compared to healthy individuals. This suggests a low grade of chronic inflammation that is the immunological feature of the ovary in PCOS patients. However, an increased risk of cancer in patients with PCOS requires further in vitro investigation of other aspects of anti-tumor responses using diverse sample size. Additional, exploring other immune cytokine profiles could be beneficial.

Background: The Human Leukocyte Antigen (HLA) is the most polymorphic region in human genome. Moreover, HLA haplotype frequencies are largely used in transplantation, the treatment of autoimmune diseases, and population-based studies. The present study aimed to determine HLA-A,-B,-DR alleles and haplotype frequencies in 88 unrelated donors of Iranian Gilak ethnic group, by Polymerase Chain Reaction with Sequence-Specific Primer (PCR-SSP) assay. The study findings were compared with previous reports on HLA alleles of different Iranian ethnics. Materials and Methods: The blood samples were collected from 88 donors of the Gilak ethnicity. Deoxyribonucleic Acid (DNA) of the samples were extracted. Then, we performed PCR and electrophoresis. The frequency of different alleles was analyzed using software. Results: Our obtained results suggested that the most frequent alleles for HLA-A were A*02 (24. 4%), A*11 (17. 6%), and A*03 (14. 2%), and the same for HLA-B were B*35 (26. 7%), B*51 (12. 5%), and B*52 (11. 4%), and for HLA-DRB1 were DRB1*11 (14. 1%), DRB1*01 (13. 5%), and DRB1*04 (11. 8%). In addition, the most common three-locus haplotypes were A02: B35: DRB01 (9. 1%), A68: B49: DRB14 (6. 2%), and A11: B51: DRB04 (5. 1%) among the studied group. Conclusion: Despite some differences, we found a strong relationship in the allelic variation between Gilak ethnicity and other Iranian and Caucasians ethnics.