Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Autophagy is required to ensure cellular homeostasis. Perturbations in autophagy have been reported to be involved in the pathogenesis of several diseases such as cancer and infection. Rheumatoid arthritis (RA) is characterized by exaggerated synovial proliferation in which interleukin-17A (IL-17A) plays a key role. The aims of this study were (1) to evaluate whether IL-17A influences on autophagic flux in the synovium of the patients with RA and (2) to investigate whether the modulation of autophagy can regulate migration and proliferation of fibroblast-like synoviocytes (FLS) from the patients with RA (RA-FLS) under inflammatory milieu.
Methods: Synovial tissue was obtained from the patients with RA or osteoarthritis (OA). FLS was cultured with IL-17A and/or autophagy regulators. The expression of marker proteins for autophagic flux (LC3B, Beclin1, Atg5, p62) and the formation of autophagolysosome (LAMP1) were analyzed by western blot and immunofluorescence study. A migration scratch assay was used to assess FLS migration in response to stimulation with IL-17A. Proliferation of FLS was determined by the viable cell count using trypan blue.
Results: LC3 conversion from LC3-Ⅰto LC3-Ⅱ was increased in RA-FLS than in OA-FLS. IL-17A upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. The accumulation of p62 was also prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by Bafilomycin A1 which prevented the formation of autophagolysosomes. P62-silencing enhanced IL-17A-induced autophagy activation in RA-FLS.
Conclusion: This study reveals that IL-17A stimulates autophagy and that intervention of autophagy can control IL-17A-induced migration and proliferation of FLS. Our results also provide additional evidence for a significant role of autophagy in the pathogenesis of RA. Thus, we suggest that autophagy might be a potential therapeutic target for the management of RA.
To cite this abstract in AMA style:Kim JM, Bang J, Jeong HJ, Son CN, Kim SH. Autophagy Alteration Affects Migration and Proliferation of Rheumatoid Arthritis Fibroblast-like Synoviocytes Stimulated By IL-17A [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/autophagy-alteration-affects-migration-and-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-stimulated-by-il-17a/. Accessed November 28, 2020.
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