Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)
Autor: | Ali Mosayebian, Roya Sherkat, Saeid Abediankenari, Monireh Golpour, Alireza Rafiei |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Iranian Journal of Basic Medical Sciences, Vol 24, Iss 10, Pp 1421-1427 (2021) |
Druh dokumentu: | article |
ISSN: | 2008-3866 2008-3874 |
DOI: | 10.22038/ijbms.2021.59180.13140 |
Popis: | 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 |
Databáze: | Directory of Open Access Journals |
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