Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to non-apoptotic cell death. Fibroblast-like synoviocytes (FLS) resistance to apoptosis is a major characteristic of rheumatoid arthritis (RA). We hypothesized that interleukin (IL)-17A might have an impact on autophagic flux and that modulation of autophagy might be involved in migration and proliferation of synovial fibroblasts in the patients with RA under inflammatory condition.
Methods: Synovial tissue was obtained from clinically involved knee joints of patients with RA or osteoarthritis (OA) patients. The autophagosome of FLS isolated from RA and OA patients displayed different morphological and physiological features by using transmission electron microscopy. The effects of IL-17 on the relationship between autophagy and cell migration were evaluated with co-treatment of autophagy inhibitor using bafilomycin A1 and transfection of si-Atg5.
Results: IL-17 induced autophagosome formation and autolysosome accumulation in RA FLS, suggesting that they were resistant to apoptosis. IL-17A increased autophagy of RA FLS by causing up-regulation of LC3II, Atg5 and Beclin1. Migration and proliferation of FLS stimulated by IL-17A was suppressed by bafilomycin A1 and si-Atg5 which knocked down of autophagy. And, autophagy inhibitor regulated signaling pathway which decreased IL-17A-induced expression of phosphorylation-Akt and increased mTOR signaling pathway.
Conclusion: Taken together, our findings demonstrated that IL-17A could induce activate autophagy, induce inflammatory response, and eventually lead to proliferation of synoviocytes. We suggest that autophagy can be one of the therapeutic target for the RA management.
To cite this abstract in AMA style:Kim SH, Bang J, Kim JM, Son CN, Chae JN, Jeong HJ. IL-17A Induced Autophagy That the Proliferation of Rheumatoid Arthritis Fibroblast-like Synoviocytes through Down-Regulation of PI3K/AKT/mTOR Signaling Pathway [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/il-17a-induced-autophagy-that-the-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-down-regulation-of-pi3kaktmtor-signaling-pathway/. Accessed June 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-17a-induced-autophagy-that-the-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-down-regulation-of-pi3kaktmtor-signaling-pathway/