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 | ||
| مراجع | ||
|
1. Azizi G, Azarian SK, Nazeri S, Mosayebian A, Ghiasy S, Sadri G, et al. Monogenic auto-inflammatory syndromes: A review of the literature. Iran J Allergy Asthma Immunol 2016:430-444. 2. Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth update on the Iranian national registry of primary immunodeficiencies: Integration of molecular diagnosis. J Clin Immunol 2018;38:816-832. 3. Portincasa P. Colchicine, biologic agents and more for the treatment of familial mediterranean fever. The old, the new, and the rare. Curr Med Chem 2016;23:60-86. 4. Van Gorp H, Saavedra PH, de Vasconcelos NM, Van Opdenbosch N, Walle LV, Matusiak M, et al. Familial mediterranean fever mutations lift the obligatory requirement for microtubules in pyrin inflammasome activation. Proc Natl Acad Sci 2016;113:14384-14389. 5. Goulielmos G, Fragouli E, Aksentijevich I, Sidiropoulos P, Boumpas D, Eliopoulos E. Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF). Biochem biophys Res Commun 2006;345:1326-1332. 6. Majeed HA, El-Khateeb M, El-Shanti H, Rabaiha ZA, Tayeh M, Najib D, et al. The spectrum of familial Mediterranean fever gene mutations in Arabs: Report of a large series. Seminars in arthritis and rheumatism; 2005: Elsevier. 7. Medlej-Hashim M, Serre J-L, Corbani S, Saab O, Jalkh N, Delague V, et al. Familial Mediterranean fever (FMF) in Lebanon and Jordan: A population genetics study and report of three novel mutations. Eur J Med Genet 2005;48:412-420. 8. Lee JH, Kim JH, Shim JO, Lee KC, Lee JW, Lee JH, et al. Familial mediterranean fever presenting as fever of unknown origin in Korea. Korean J Pediatr 2016;59:53-56. 9. Corsia A, Georgin-Lavialle S, Hentgen V, Hachulla E, Grateau G, Faye A, et al. A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever. Orphanet J Rare Dis 2017;12:54. 10. Slobodnick A, Shah B, Pillinger MH, Krasnokutsky S. Colchicine: Old and new. Am J med 2015;128:461-470. 11. Twig G, Livneh A, Vivante A, Afek A, Shamiss A, Derazne E, et al. Mortality risk factors associated with familial mediterranean fever among a cohort of 1.25 million adolescents. Ann Rheum Dis 2014; 73:704-709. 12. Ter Haar N, Lachmann H, Özen S, Woo P, Uziel Y, Modesto C, et al. Treatment of autoinflammatory diseases: Results from the Eurofever Registry and a literature review. Ann Rheum Dis 2013; 72:678-685. 13. Brucato A, Imazio M, Gattorno M, Lazaros G, Maestroni S, Carraro M, et al. Effect of anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized clinical trial. JAMA 2016;316:1906-1912. 14. Yang W-S, Xin Y, Sun S, Li X-M. The role of parthenolide in the inhibition of proliferation and regulation of apoptosis of the human cervical carcinoma HeLa cells. Int J Clin Exp Med 2016;9:19231-19237. 15. D’Anneo A, Carlisi D, Lauricella M, Emanuele S, Di Fiore R, Vento R, et al. Parthenolide induces caspase‐independent and AIF‐mediated cell death in human osteosarcoma and melanoma cells. J Cell Physiol 2013;228:952-967. 16. Baldwin AG, Brough D, Freeman S. Inhibiting the inflammasome: A chemical perspective. J Med Chem 2015;59:1691-1710. 17. Guzman ML, Rossi RM, Neelakantan S, Li X, Corbett CA, Hassane DC, et al. An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood, J Am Soc Hematol 2007;110:4427-4435. 18. Fattahi S, Langroudi MP, Samadani AA, Nikbakhsh N, Asouri M, Akhavan-Niaki H. Application of unique sequence index (USI) barcode to gene expression profiling in gastric adenocarcinoma. J Cell Commun Signal 2017;11:97-104. 19. Li S, Gao X, Wu X, Wu Z, Cheng L, Zhu L, et al. Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells. Acta Biochim Biophys Sin 2015;47:368-375. 20. Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu J-W, et al. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem 2010;285:9792-802. 21. Jamilloux Y, Lefeuvre L, Magnotti F, Martin A, Benezech S, Allatif O, et al. Familial mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome. Rheumatol 2018;57:100-111. 22. Bren GD, Solan NJ, Miyoshi H, Pennington KN, Pobst LJ, Paya CV. Transcription of the RelB gene is regulated by NF-kappaB. Oncogene 2001;20:7722-7733. 23. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, et al. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood 2008;112:1794-1803. 24. Flores-Lopez G, Moreno-Lorenzana D, Ayala-Sanchez M, Aviles-Vazquez S, Torres-Martinez H, Crooks PA, et al. Parthenolide and DMAPT induce cell death in primitive CML cells through reactive oxygen species. J Cellular Mol Med 2018;22:4899-4912. 25. Yip-Schneider MT, Wu H, Stantz K, Agaram N, Crooks PA, Schmidt CM. Dimethylaminoparthenolide and gemcitabine: A survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer 2013;13:194. 26. Zhang M, Liu R-T, Zhang P, Zhang N, Yang C-L, Yue L-T, et al. Parthenolide inhibits the initiation of experimental autoimmune neuritis. J Neuroimmunol 2017;305:154-161. 27. Yip-Schneider MT, Wu H, Njoku V, Ralstin M, Holcomb B, Crooks PA, et al. Effect of celecoxib and the novel anti-cancer agent, dimethylamino-parthenolide, in a developmental model of pancreatic cancer. Pancreas 2008;37:45-53. 28. Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, et al. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood 2005;105:4163-4169. 29. Kim SL, Liu YC, Seo SY, Kim SH, Kim IH, Lee SO, et al. Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling. Oncol Lett 2015;9:2135-2142. 30. Viennois E, Xiao B, Ayyadurai S, Wang L, Wang PG, Zhang Q, et al. Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer. Lab Invest 2014;94:950-965. 31. de Carvalho LSA, Fontes LBA, Gazolla MC, dos Santos Dias D, Juliano MA, Macedo GC, et al. Parthenolide modulates immune response in cells from C57BL/6 mice induced with experimental autoimmune encephalomyelitis. Planta Medica 2017;83:693-700. | ||
|
آمار تعداد مشاهده مقاله: 673 تعداد دریافت فایل اصل مقاله: 414 |
||