LinkedIn

 آمار

تعداد نشریات20
تعداد شماره‌ها1,095
تعداد مقالات10,041
تعداد مشاهده مقاله28,016,720
تعداد دریافت فایل اصل مقاله7,812,616
Kazemi, Romina, Mohammadi, Mobin, Salimiyan, Samira, Aliakbari, Sara, Ahmadi, Moslem, Rahmani, Mohammad. (1402). Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells. سامانه مدیریت نشریات علمی, 20(2), 219-231. doi: 10.22034/iji.2023.95659.2385
Romina Kazemi; Mobin Mohammadi; Samira Salimiyan; Sara Aliakbari; Moslem Ahmadi; Mohammad Reza Rahmani. "Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells". سامانه مدیریت نشریات علمی, 20, 2, 1402, 219-231. doi: 10.22034/iji.2023.95659.2385
Kazemi, Romina, Mohammadi, Mobin, Salimiyan, Samira, Aliakbari, Sara, Ahmadi, Moslem, Rahmani, Mohammad. (1402). 'Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells', سامانه مدیریت نشریات علمی, 20(2), pp. 219-231. doi: 10.22034/iji.2023.95659.2385
Kazemi, Romina, Mohammadi, Mobin, Salimiyan, Samira, Aliakbari, Sara, Ahmadi, Moslem, Rahmani, Mohammad. Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells. سامانه مدیریت نشریات علمی, 1402; 20(2): 219-231. doi: 10.22034/iji.2023.95659.2385

Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells

Iranian Journal of Immunology
مقاله 8، دوره 20، شماره 2، شهریور 2023، صفحه 219-231    اصل مقاله (1.47 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22034/iji.2023.95659.2385
نویسندگان
Romina Kazemi1، 2؛ Mobin Mohammadi2، 3؛ Samira Salimiyan1، 2؛ Sara Aliakbari2؛ Moslem Ahmadi4؛ Mohammad Reza Rahmani* 2، 5
1Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
2Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
3Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
4Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
5Zoonosis Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
چکیده
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.
کلیدواژه‌ها
Adipose-Derived Mesenchymal Stem Cells؛ Immunomodulation؛ Inflammatory Response؛ LDN؛ Naltrexone
مراجع
  1. Sharma RR, Pollock K, Hubel A, McKenna D. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion. 2014;54(5):1418-37.
  2. Dazzi F, Krampera M. Mesenchymal stem cells and autoimmune diseases. Best Practice & Research Clinical Haematology. 2011;24(1):49-57.
  3. Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nature immunology. 2014;15(11):1009-16.
  4. Moura FCd, Martins CdS, Soares PM, Brito GAdC. Low-Dose naltrexone in diseases’ treatment: global review. 2016.
  5. Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Medical hypotheses. 2009;72(3):333-7.
  6. Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy. International immunopharmacology. 2018;61:178-84.
  7. Meng J, Meng Y, Plotnikoff NP, Youkilis G, Griffin N, Shan F. Low dose naltrexone (LDN) enhances maturation of bone marrow dendritic cells (BMDCs). International immunopharmacology. 2013;17(4):1084-9.
  8. Yi Z, Guo S, Hu X, Wang X, Zhang X, Griffin N, et al. Functional modulation on macrophage by low dose naltrexone (LDN). International immunopharmacology. 2016;39:397-402.
  9. McLaughlin PJ, McHugh DP, Magister MJ, Zagon IS. Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis. BMC immunology. 2015;16(1):1-11.
  10. Matters GL, Harms JF, McGovern C, Fitzpatrick L, Parikh A, Nilo N, et al. The opioid antagonist naltrexone improves murine inflammatory bowel disease. Journal of immunotoxicology. 2008;5(2):179-87.
  11. Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low‐dose naltrexone and quality of life in multiple sclerosis. Annals of neurology. 2010;68(2):145-50.
  12. Chopra P, Cooper MS. Treatment of complex regional pain syndrome (CRPS) using low dose naltrexone (LDN). Journal of Neuroimmune Pharmacology. 2013;8(3):470-6.
  13. Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn's disease. American Journal of Gastroenterology. 2007;102(4):820-8.
  14. Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. Biomedicines. 2017;5(2):16.
  15. Holan V, Cechova K, Zajicova A, Kossl J, Hermankova B, Bohacova P, et al. The impact of morphine on the characteristics and function properties of human mesenchymal stem cells. Stem Cell Reviews and Reports. 2018;14(6):801-11.
  16. Mohammadi M, Mohammadi M, Rezaee MA, Ghadimi T, Abolhasani M, Rahmani MR. Effect of gestational age on migration ability of the human umbilical cord vein mesenchymal stem cells. Advances in medical sciences. 2018;63(1):119-26.
  17. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, et al. IFN‐γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. European journal of immunology. 2008;38(6):1745-55.
  18. Sacerdote P. Opioids and the immune system. Palliative medicine. 2006;20(8_suppl):9-15.
  19. Liang X, Liu R, Chen C, Ji F, Li T. Opioid system modulates the immune function: a review. Translational perioperative and pain medicine. 2016;1(1):5.
  20. Eisenstein TK. The Role of Opioid Receptors in Immune System Function. Frontiers in Immunology. 2019;10:2904.
  21. Galeotti N, Stefano GB, Guarna M, Bianchi E, Ghelardini C. Signaling pathway of morphine induced acute thermal hyperalgesia in mice. Pain. 2006;123(3):294-305.
  22. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical rheumatology. 2014;33(4):451-9.
  23. Toljan K, Vrooman B. Low-dose naltrexone (LDN)—review of therapeutic utilization. Medical Sciences. 2018;6(4):82.
  24. Aliakbari S, Mohammadi M, Rezaee MA, Amini AA, Fakhari S, Rahmani MR. Impaired immunomodulatory ability of type 2 diabetic adipose-derived mesenchymal stem cells in regulation of inflammatory condition in mixed leukocyte reaction. EXCLI journal. 2019;18:852.
  25. Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, et al. Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy. 2009;11(5):570-83.
  26. Sheng H, Wang Y, Jin Y, Zhang Q, Zhang Y, Wang L, et al. A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell research. 2008;18(8):846-57.
  27. Augello A, Tasso R, Negrini SM, Amateis A, Indiveri F, Cancedda R, et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. European journal of immunology. 2005;35(5):1482-90.
  28. English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-γ and TNF-α differentially regulate immunomodulation by murine mesenchymal stem cells. Immunology letters. 2007;110(2):91-100.
  29. Li D, Han Y, Zhuang Y, Fu J, Liu H, Shi Q, et al. Overexpression of COX-2 but not indoleamine 2, 3-dioxygenase-1 enhances the immunosuppressive ability of human umbilical cord-derived mesenchymal stem cells. International Journal of Molecular Medicine. 2015;35(5):1309-16.
  30. Ohno Y, Ohno S, Suzuki N, Kamei T, Inagawa H, Soma GI, et al. Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma. International journal of cancer. 2005;114(5):696-701.
  31. Kota DJ, Prabhakara KS, Toledano‐Furman N, Bhattarai D, Chen Q, DiCarlo B, et al. Prostaglandin E2 indicates therapeutic efficacy of mesenchymal stem cells in experimental traumatic brain injury. Stem Cells. 2017;35(5):1416-30.
  32. Maraldi T, Beretti F, Guida M, Zavatti M, De Pol A. Role of hepatocyte growth factor in the immunomodulation potential of amniotic fluid stem cells. Stem cells translational medicine. 2015;4(6):539-47.
  33. Chen PM, Liu KJ, Hsu PJ, Wei CF, Bai CH, Ho LJ, et al. Induction of immunomodulatory monocytes by human mesenchymal stem cell‐derived hepatocyte growth factor through ERK1/2. Journal of leukocyte biology. 2014;96(2):295-303.
  34. Ryan J, Barry F, Murphy J, Mahon BP. Interferon‐γ does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clinical & Experimental Immunology. 2007;149(2):353-63.
  35. Liang C, Jiang E, Yao J, Wang M, Chen S, Zhou Z, et al. Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro. Hematology. 2018;23(1):44-9.
  36. Rubtsov Y, Goryunov К, Romanov А, Suzdaltseva Y, Sharonov G, Tkachuk V. Molecular mechanisms of immunomodulation properties of mesenchymal stromal cells: a new insight into the role of ICAM-1. Stem cells international. 2017;2017.
  37. Liang C, Chen S, Wang M, Zhai W, Zhou Z, Pang A, et al. Synergistic immunomodulatory effects of interferon-gamma and bone marrow mesenchymal stem cells. Zhonghua xue ye xue za zhi= Zhonghua xueyexue zazhi. 2013;34(3):213.
  38. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nature immunology. 2015;16(5):448-57.
  39. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. The Journal of Immunology. 2006;177(4):2080-7.
  40. Van Buul G, Villafuertes E, Bos P, Waarsing J, Kops N, Narcisi R, et al. Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture. Osteoarthritis and Cartilage. 2012;20(10):1186-96.
  41. Ludwig MD, Zagon IS, McLaughlin PJ. Featured article: modulation of the OGF–OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis. Experimental Biology and Medicine. 2018;243(4):361-9.
  42. Bao W, Wang Y, Fu Y, Jia X, Li J, Vangan N, et al. mTORC1 regulates flagellin-induced inflammatory response in macrophages. PLoS One. 2015;10(5):e0125910.
  43. Kim H, Chen L, Lim G, Sung B, Wang S, McCabe MF, et al. Brain indoleamine 2, 3-dioxygenase contributes to the comorbidity of pain and depression. The Journal of clinical investigation. 2012;122(8).
  44. Li F, Wei L, Li S, Liu J. Indoleamine-2, 3-dioxygenase and Interleukin-6 associated with tumor response to neoadjuvant chemotherapy in breast cancer. Oncotarget. 2017;8(64):107844.
  45. Zhang W, Zhang J, Zhang Z, Guo Y, Wu Y, Wang R, et al. Overexpression of indoleamine 2, 3-dioxygenase 1 promotes epithelial-mesenchymal transition by activation of the IL-6/STAT3/PD-L1 pathway in bladder cancer. Translational oncology. 2019;12(3):485-92.
  46. Zhang W, Liu Y, Yan Z, Yang H, Sun W, Yao Y, et al. IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma. Journal for immunotherapy of cancer. 2020;8(1).
  47. Li Z, Zhang C, Du J-X, Zhao J, Shi M-T, Jin M-W, et al. Adipocytes promote tumor progression and induce PD-L1 expression via TNF-α/IL-6 signaling. Cancer Cell International. 2020;20:1-9.
  48. Jin Y-H, Hou W, Kang HS, Koh C-S, Kim BS. The role of interleukin-6 in the expression of PD-1 and PDL-1 on central nervous system cells following infection with Theiler's murine encephalomyelitis virus. Journal of virology. 2013;87(21):11538-51.
  49. Weber R, Groth C, Lasser S, Arkhypov I, Petrova V, Altevogt P, et al. IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy. Cellular Immunology. 2021;359:104254.
  50. de Araújo Farias V, Carrillo-Gálvez AB, Martín F, Anderson P. TGF-β and mesenchymal stromal cells in regenerative medicine, autoimmunity and cancer. Cytokine & Growth Factor Reviews. 2018;43:25-37.
  51. Han G, Li F, Singh TP, Wolf P, Wang X-J. The pro-inflammatory role of TGFβ1: a paradox? International journal of biological sciences. 2012;8(2):228.
  52. Walia B, Wang L, Merlin D, Sitaraman SV. TGF‐β down‐regulates IL‐6 signaling in intestinal epithelial cells: Critical role of SMAD‐2. The FASEB journal. 2003;17(14):1-20.
  53. Ohta K, Yamagami S, Taylor AW, Streilein JW. IL-6 antagonizes TGF-β and abolishes immune privilege in eyes with endotoxin-induced uveitis. Investigative ophthalmology & visual science. 2000;41(9):2591-9.
آمار
تعداد مشاهده مقاله: 828
تعداد دریافت فایل اصل مقاله: 613


سامانه مدیریت نشریات علمی. قدرت گرفته از سیناوب