Mosayebian, Ali, Sherkat, Roya, Abediankenari, Saeid, Golpour, Monireh, Rafiei, Alireza. (1400). Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF). , 24(10), 1421-1427. doi: 10.22038/ijbms.2021.59180.13140
Ali Mosayebian; Roya Sherkat; Saeid Abediankenari; Monireh Golpour; Alireza Rafiei. "Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)". , 24, 10, 1400, 1421-1427. doi: 10.22038/ijbms.2021.59180.13140
Mosayebian, Ali, Sherkat, Roya, Abediankenari, Saeid, Golpour, Monireh, Rafiei, Alireza. (1400). 'Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)', , 24(10), pp. 1421-1427. doi: 10.22038/ijbms.2021.59180.13140
Mosayebian, Ali, Sherkat, Roya, Abediankenari, Saeid, Golpour, Monireh, Rafiei, Alireza. Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF). , 1400; 24(10): 1421-1427. doi: 10.22038/ijbms.2021.59180.13140

Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF)

Iranian Journal of Basic Medical Sciences
دوره 24، شماره 10، دی 2021، صفحه 1421-1427    اصل مقاله (1.17 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2021.59180.13140
نویسندگان
Ali Mosayebian1؛ Roya Sherkat2؛ Saeid Abediankenari3؛ Monireh Golpour4؛ Alireza Rafiei* 1
1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of medical sciences, Sari, Iran
4Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Science, Sari, Iran
چکیده
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.
کلیدواژه‌ها
CASP1؛ Dimethylamino-arthenolide؛ Familial Mediterranean Fever؛ IL-1β؛ IL-18؛ MEFV؛ NFκB؛ NLRP3
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