Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)
Publish Year: 1400
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:
JR_IJBMS-24-10_013
تاریخ نمایه سازی: 11 مهر 1400
Abstract:
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-۱β (IL-۱β) and interleukin-۱۸ (IL-۱۸), leading to excess inflammation. Colchicine is a common drug widely used for treatment of FMF attacks, but about ۵–۱۵% 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 ۳ (NLRP۳), and cysteine-aspartic acid protease ۱(Caspase-۱) 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, NLRP۳, MEFV, CASP۱, and IL-۱β mRNA were investigated using a TaqMan real-time PCR, and the protein levels of IL-۱β, IL-۱۸, and IL-۳۷ were assessed via an enzyme-linked immunosorbent assay (ELISA) in LPS/ ATP-stimulated PBMCs.Results: DMAPT decreased the expression levels of NFκB (۰.۳۸±۰.۰۹۶, P<۰.۰۰۰۱), NLRP۳ (۰.۳۹±۰.۱۲, P<۰.۰۰۱), MEFV (۰.۳۸۴±۰.۱۴۵, P<۰.۰۰۱), CASP۱ (۰.۴۸±۰.۱۳, P=۰.۰۰۲۳), and IL-۱β (۰.۰۹±۰.۰۹, P<۰.۰۰۰۱) and reduced the secretion levels of IL-۱β (۸.۹۲±۵.۳ vs. ۱۴۹.۸۵±۲۰.۹۲, P<۰.۰۰۰۱), IL-۱۸ (۱۳۵±۳۲.۱ vs. ۱۹۲±۲۲.۱۸, P=۰.۰۱), and IL-۳۷ (۲۷.۵±۶.۳ vs. ۷۸.۱۹±۱۴.۳, P<۰.۰۰۰۱) 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.
Keywords:
CASP۱ , Dimethylamino-arthenolide , Familial Mediterranean fever , IL-۱β , IL-۱۸ , MEFV , NFκB , NLRP۳
Authors
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
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