ORIGINAL_ARTICLE
Tumor Associated Mesenchymal Stromal Cells Show Higher Immunosuppressive and Angiogenic Properties Compared to Adipose Derived MSCs
Background: Differentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells. Objective: To characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (T-MSCs) isolated from mammary tumors of BALB/c mice. Methods: Immunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Realtime PCR, respectively. Results: T-MSCs expressed significantly higher levels of HLADR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in TMSCs (p=0.07 and p=0.00, respectively). Additionally, T-MSCs expressed higher levels of iNOS and MMP9 (p=0.01 and p=0.01, respectively). T-MSCs were also able to induce higher levels of proliferation and migration of HUVEC endothelial cells in wound scratch assay compared to AD-MSCs (p=0.015). Conclusion: Functional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.
https://iji.sums.ac.ir/article_16752_d84d806bc2cd96fa325eb07adc3d33a6.pdf
2015-12-01
226
239
Adipose-Derived Mesenchymal Stromal Cells
Breast cancer
Immunomodulatory Properties
Tumoral-MSCs
Ladan
Langroudi
1
Department of Immunology
AUTHOR
Zuhair Muhammad
Hassan
hasan_zm@modares.ac.ir
2
Department of Immunology
LEAD_AUTHOR
Masoud
Soleimani
3
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University
AUTHOR
Seyed Mahmoud
Hashemi
4
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
ORIGINAL_ARTICLE
Altered Suppressor Function of Regulatory T Cells in Type 1 Diabetes
Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in comparison with healthy controls. Methods: Fifteen new cases of T1D patients and 15 age- and sexmatched healthy controls were recruited to this study. Their peripheral blood mononuclear cells (PBMCs) were isolated and CD4 +CD25+FoxP3+CD127-/low Treg cells were studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic- Activated Cell Separation (MACS) technology and by using CFSE (carboxyfluorescein succinimidyl ester) dilution assay, their suppressive activity was evaluated in the coculture of CD4 +CD25- T responder cells with Treg cells. Results: The percentage of CD4 +CD25+FoxP3+CD127-/low Tregs did not differ between T1D patients and healthy controls but the MFI (mean fluorescence intensity) of transcription factor FoxP3 (forkhead box protein P3) was significantly decreased in T1D patients (20.03 ± 1.4 vs. 31.33 ± 2.95, p=0.0017). Moreover, the suppressive function of CD4 +CD25+CD127-/low Treg cells was significantly diminished in T1D patients in comparison with control group (35.16 ± 4.93% vs. 60.45 ± 5.26%, respectively, p=0.0015). Conclusion: Present study indicates an impaired immune regulation among T1D patients, characterized by defects in suppressive function and expression of FoxP3 in Treg cells without any significant decrease in their frequency in peripheral blood.
https://iji.sums.ac.ir/article_16753_babc63ff6b42a4cd066e054e8cdad6fe.pdf
2015-12-01
240
251
Regulatory T Cells (Tregs)
Suppressive Function
(T1D)
Type 1 Diabetes
Babak
Aghili
1
Department of Immunology, School of Medicine
AUTHOR
Ali Akbar
Amirzargar
amirzara@tums.ac.ir
2
Department of Immunology, School of Medicine
LEAD_AUTHOR
Asadollah
Rajab
3
Department of Endocrinology, Iranian Diabetes Association
AUTHOR
Ali
Rabbani
4
Growth and Development Center, Tehran University of Medical Sciences, Children's Medical Center
AUTHOR
Arya
Sotoudeh
5
Growth and Development Center, Tehran University of Medical Sciences, Children's Medical Center
AUTHOR
Sara
Assadiasl
6
Department of Immunology, School of Medicine
AUTHOR
Bagher
Larijani
7
Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Ahmad
Massoud
8
Department of Immunology, School of Medicine
AUTHOR
ORIGINAL_ARTICLE
Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double- Blind Placebo-Controlled Study
Background: Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1 a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. Objectives: To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. Methods: The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL- 17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. Results: Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p <0.05). Conclusion: Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.
https://iji.sums.ac.ir/article_16754_cca2542cff564277f9130dda82b85b9e.pdf
2015-12-01
252
262
Paternal Lymphocyte Therapy
Recurrent Miscarriage
Regulatory T
Cell
T Helper 17
Vitamin D3
Mitra
Rafiee
1
Department of Immunology, School of Medicine
AUTHOR
Marjan
Gharagozloo
2
Department of Immunology, School of Medicine
AUTHOR
Ataollah
Ghahiri
3
Department of Gynecology and Obstetrics, Al-Zahra University Hospital
AUTHOR
Ferdous
Mehrabian
4
Department of Gynecology and Obstetrics, Al-Zahra University Hospital
AUTHOR
Mohammad R.
Maracy
5
Department of Community Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
AUTHOR
Shirin
Kouhpayeh
6
Department of Immunology, School of Medicine
AUTHOR
Ina Laura
Pieper
7
Institute of Life Science, College of Medicine, Swansea University, Swansea, United Kingdom
AUTHOR
Abbas
Rezaei
rezaei@mui.ac.ir
8
Department of Immunology, School of Medicine
LEAD_AUTHOR
ORIGINAL_ARTICLE
H2-EB1 Molecule Alleviates Allergic Rhinitis Symptoms of H2-Eb1 Knockout Mice
Background: H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis. Objective: To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR. Methods: The Cre/LoxP system and ES gene knockout technology were applied to create heterozygous H2-Eb1 (+/-) knockout mice and their offspring of knockout homozygous(-/-), heterozygous (+/-) and wild type (+/+) H2-Eb1 mice. After identification, offspring of heterozygous (+/-) and homozygous (-/-) H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of H2-Eb1 in AR pathogenesis. Results: The H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous ( -/-) H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN-γ levels significantly dropped (p<0.05) in the experimental groups. For the two experimental groups, the homozygous ( -/-) mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-γ levels than their heterozygous (+/-) counterparts (p<0.05), concomitant with slighter allergic symptoms (gentle behavior and less eosinophils in nasal mucosa). Conclusion: Our study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR.
https://iji.sums.ac.ir/article_16755_bf98235bce7d127cd11a84d0dbfad677.pdf
2015-12-01
263
273
H2-Eb1
Allergic Rhinitis
Knockout
Th1
Th2
Linge
Li
1
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Bin
Hu
2
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Juan
Feng
3
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Yu
Zhang
4
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Xi
Shou
5
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Yu
Tian
6
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Chunrong
Jiang
7
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
AUTHOR
Hua
Zhang
huazhangxjmc@163.com
8
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China
LEAD_AUTHOR
ORIGINAL_ARTICLE
Cationic Immune Stimulating Complexes Containing Soluble Leishmania Antigens: Preparation, Characterization and in Vivo Immune Response Evaluation
Background: Cationic immune stimulating complexes (PLUSCOMs) are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes (ISCOMs) derivatives and are able to elicit in vivo T cell responses against an antigen. Objective: To evaluate the effects of PLUSCOMs containing Leishmaniamajor antigens (SLA) on the type of immune response generated in the murine model of leishmaniasis. Methods: PLUSCOMs consisting of 1, 2-dioleoyl-3- trimethylammonium-propane (DOTAP) were used as antigen delivery system/immunoadjuvants for soluble SLA. BALB/c mice were immunized subcutaneously, three times in 2-week intervals. Footpads swellings at the site of challenge and parasite loads were assessed as a measure of protection. The immune responses were also evaluated by determination of IgG subclasses and the level of IFN- γ and IL-4 in cultured splenocytes. Results: There was no significant difference (p<0.05) between the sizes of lesions in mice immunized with different formulations. Also, there was no significant difference in the number of parasites in the footpad or spleen of all groups compared with the control group. The highest level of IFN- γ secretion was observed in the splenocytes of mice immunized with PLUSCOM/SLA (p<0.001) and lower amounts of IL-4 was observed in PLUSCOM group (p<0.001) as compared to negative control. Conclusion: Our results indicated that SLA in different formulations generated an immune response with mixed Th1/Th2 response that was not protective enough despite the activation of CD4 + T cells with secreting IFN-γ in groups which received PLUSCOM with antigen.
https://iji.sums.ac.ir/article_16756_a19544af098ebecf6aedef1c607c0d7b.pdf
2015-12-01
274
287
Leishmania Major
Nanoparticle
PLUSCOM
Vaccine
Ahmad
Mehravaran
1
Nanotechnology Research Center, School of Pharmacy
AUTHOR
Mahmoud Reza
Jaafari
2
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad
AUTHOR
Seyed Amir
Jalali
3
Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences
AUTHOR
Ali
Khamesipour
4
Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Mohsen
Tafaghodi
5
Nanotechnology Research Center, School of Pharmacy
AUTHOR
Mansure
Hojatizade
6
Nanotechnology Research Center, School of Pharmacy
AUTHOR
Azam
Abbasi
7
Nanotechnology Research Center, School of Pharmacy
AUTHOR
Ali
Badiee
badieea@mums.ac.ir
8
Nanotechnology Research Center, School of Pharmacy
LEAD_AUTHOR
ORIGINAL_ARTICLE
Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Seraand Central Nervous System of EAEMice
Background: IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. Objective: To evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE. Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA. Results: The mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL- 17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively). In 200 mg/kg gingertreated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL- 23 levels were significantly decreased as compared to PBS-treated EAE mice (p<0.05, p<0.001, p<0.001 and p<0.05, respectively). Moreover, 300 mg/kg ginger-treated EAE group had significantly lower expression of IL-17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (p<0.02, p<0.001, p<0.001, p<0.03 and p<0.004, respectively). Conclusion: Ginger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies.
https://iji.sums.ac.ir/article_16757_bb1d1b4d9b78c8f85fe4a55482f0115c.pdf
2015-12-01
288
301
Experimental Autoimmune Encephalomyelitis
Ginger
IL-17
IL-23
Abdollah
Jafarzadeh
jafarzadeh14@yahoo.com
1
Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan
LEAD_AUTHOR
Sayyed-Vahab
Azizi
2
Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman
AUTHOR
Maryam
Nemati
3
Neuroscience Research Center, Department of Neurology
AUTHOR
Hossain
Khoramdel-Azad
4
Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman
AUTHOR
Ali
Shamsizadeh
5
Department of Physiology, Medical School
AUTHOR
Fatemeh
Ayoobi
6
Department of Physiology, Medical School
AUTHOR
Zahra
Taghipour
7
Department of Histology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan
AUTHOR
Zuhair-Mohammad
Hassan
8
Department of Immunology, Medical School, Tarbiat Moddares University, Tehran, Iran
AUTHOR
ORIGINAL_ARTICLE
Serum Levels of Monocyte Chemoattractant Protein-1 Correlate with Poor Clinical Grades in Cerebral Aneurysms
Background : Ruptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte ChemoattractantProtein-1 (MCP-1) is suggested. Objective: To measure the serum level of MCP-1 in ruptured CAs in different time intervals . Methods: We measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay. Results: Mean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7 th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089). Conclusion: Our results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation.
https://iji.sums.ac.ir/article_16758_7f8968744067617abe9cb5c4ddbf5ae1.pdf
2015-12-01
302
310
Intracranial Aneurysm
Level
Monocyte Chemoatractic Protein 1
serum
Abdolkarim
Rahmanian
1
Department of Neurosurgery
AUTHOR
Navideh
Mohebali
2
Department of Neurosurgery
AUTHOR
Ali
Haghnegahdar
3
Department of Neurosurgery
LEAD_AUTHOR
Eskandar
Kamali Sarvestani
4
Department of Immunology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
Ali
Razmkon
5
Department of Neurosurgery
AUTHOR
Juri
Kivelev
6
Department of Neurosurgery, Helsinki University Central Hospital, Topeliuksenkatu, Finland
AUTHOR
Fahim
Baghban
7
Department of Neurosurgery
AUTHOR
ORIGINAL_ARTICLE
The Effect of Plasma Exchange on the Expression of FOXP3 and RORC2 in Relapsed Multiple Sclerosis Patients
Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard treatment in many other neuro-immune disorders. Recent data suggest that Treg/Th17 counterbalance may indicate the boundaries between promotion and regulation of inflammatory responses in MS and Treg/Th17 ratio may be useful as a marker for monitoring the efficiency of MS therapies. Objective: To evaluate the effect of PE on the frequency and ratio of Treg/Th17 cells through concomitant measurement of the expression levels of Treg and Th17 lineage specific transcription factors, FOXP3 and RORC2, respectively. Methods: Peripheral blood mononuclear cells of 8 relapsed MS patients were obtained before and after a complete course of PE therapy and the FOXP3 and RORC2 mRNA levels were assayed using real-time PCR approach. Results: No significant change in the expression levels of individual transcription factors existed, but a significant increase in FOXP3/RORC2 ratio (p=0.036) was observed. Conclusions: Our results suggest that PE therapy influences Treg/Th17 ratio and this maybe a mechanism by which this procedure exerts its improving effects in MS disease.
https://iji.sums.ac.ir/article_16759_b6e3bd186912b195c1001a1dbe461177.pdf
2015-12-01
311
318
Multiple Sclerosis
Plasma Exchange
Th17
Treg
Azam
Jamshidian
1
Department of Microbiology and Immunology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord
AUTHOR
Mohammad
Kazemi
2
Department of Genetic and Molecular Biology
AUTHOR
Vahid
Shaygannejad
3
Department of Neurology, School of Medicine
AUTHOR
Mansoor
Salehi
m_salehi@med.mui.ac.ir
4
Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
LEAD_AUTHOR