Background and aims Rheumatoid arthritis (RA) is characterised by exaggerated synovial proliferation in which interleukin-17A (IL-17A) plays a key role. Recently several evidences support the implication of autophagy in the pathogenesis of RA. The aims of this study are (1) to evaluate whether IL-17A influences on autophagic flux in RA synovium 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 FLS from the patients with RA or osteoarthritis (OA) were cultured with IL-17A and/or autophagy regulators. The expression of marker proteins for autophagic flux or the formation of autophagolysosome was analysed by western blot or immunofluorescence study. A migration scratch assay was used to assess FLS migration. Proliferation of FLS was determined by the viable cell count using trypan blue.
Results LC3 conversion from LC3-I to 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.
Conclusions 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.
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