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Iranian Journal of Basic Medical Sciences، جلد ۲۴، شماره ۱۰، صفحات ۱۴۲۱-۱۴۲۷
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عنوان انگلیسی Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)
چکیده انگلیسی مقاله Objective(s): Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disorder that is caused by mutations in the Mediterranean fever (MEFV) gene and is associated with an increase in pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), leading to excess inflammation. Colchicine is a common drug widely used for treatment of FMF attacks, but about 5–15% of the patients show resistance to the regular colchicine treatment. In this study, we used dimethylamino-parthenolide (DMAPT), as a small molecule inhibitor of Nuclear factor-κB (NF-κB), NLR family Pyrin domain containing 3 (NLRP3), and cysteine-aspartic acid protease 1(Caspase-1) on FMF-derived peripheral blood mononuclear cells (PBMCs).Materials and Methods: The effects of DMAPT and colchicine on metabolic activity and apoptosis of FMF-derived PBMCs were evaluated by MTT and Annexin V/PI assays, respectively. Also, the expression levels of NF-κB, NLRP3, MEFV, CASP1, and IL-1β mRNA were investigated using a TaqMan real-time PCR, and the protein levels of IL-1β, IL-18, and IL-37 were assessed via an enzyme-linked immunosorbent assay (ELISA) in LPS/ ATP-stimulated PBMCs.Results: DMAPT decreased the expression levels of NFκB (0.38±0.096, P< 0.0001), NLRP3 (0.39±0.12, P< 0.001), MEFV (0.384±0.145, P< 0.001), CASP1 (0.48±0.13, P=0.0023), and IL-1β (0.09±0.09, P< 0.0001) and reduced the secretion levels of IL-1β (8.92±5.3 vs. 149.85±20.92, P< 0.0001), IL-18 (135±32.1 vs. 192±22.18, P=0.01), and IL-37 (27.5±6.3 vs. 78.19±14.3, P< 0.0001) as compared to untreated cells.Conclusion: Given the obtained results in comparison with previous research, the future clinical development of DMAPT could result in the expansion of new anti-inflammatory therapeutics for FMF disorder.
کلیدواژه‌های انگلیسی مقاله CASP1, Dimethylamino-arthenolide, Familial Mediterranean fever, IL-1β, IL-18, MEFV, NFκB, NLRP3
نویسندگان مقاله | Ali Mosayebian
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran


| Roya Sherkat
Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


| Saeid Abediankenari
Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of medical sciences, Sari, Iran


| Monireh Golpour
Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Science, Sari, Iran


| Alireza Rafiei
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
نشانی اینترنتی https://ijbms.mums.ac.ir/article_18803.html
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