Abstract
The synovial intimal lining is mainly governed by fibroblast-like synoviocytes (FLS), which portray a transformed tumor-like phenotype in rheumatoid arthritis (RA). Among the diverse cytokines that engender FLS, interleukin-21 (IL-21) was reported to stimulate hyperproliferation and perpetuate inflammation. Recently, choline kinase (ChoKα) has been reported to be an essential enzyme aiding RA-FLS hyperproliferation by altering phosphatidylcholine biosynthesis. The current study aimed to elucidate the therapeutic efficacy of myricetin, a flavonoid, in abating the IL-21-induced tumor-like phenotype of adjuvant-induced arthritis (AIA)-FLS via the ChoKα signaling cascade. Our results showed that myricetin suppressed IL-21 receptor expression and activation of the ChoKα signaling cascade (N-Ras, Ral-GDS, and PI3K) in IL-21-induced AIA-FLS. Consequently, myricetin treatment decreased ChoKα and PLD2 enzymatic activity and inhibited the proliferative, migratory, and invasive properties of AIA-FLSs. Our results demonstrated that myricetin could be a promising anti-arthritic compound by abating IL-21-induced hyperproliferation, migration, and invasive behavior of AIA-FLS by downregulating the ChoKα signaling cascade.
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Ann Miriam Jose designed the research, conducted the study, and drafted the manuscript. Mahaboobkhan Rasool supervised the study and drafted the final manuscript.
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All experiments were certified and reviewed by the Institutional Animal Ethical Committee (IAEC) members with approval number (vide registration no: VIT/IAEC/20/DEC2021/15). All experimental procedures were performed according to the guidelines proposed by the Committee for Control and Supervision of Experiments on Animals (CPCSEA) in New Delhi, India.
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Jose, A.M., Rasool, M. Myricetin ameliorates the IL-21-induced tumorigenic phenotype of adjuvant-induced arthritis FLS by modulating the choline kinase signaling cascade. In Vitro Cell.Dev.Biol.-Animal 59, 811–820 (2023). https://doi.org/10.1007/s11626-023-00827-6
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DOI: https://doi.org/10.1007/s11626-023-00827-6