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AB0093 Regulation of Autophagic Flux Alters Interleukin-17A-Induced Migration and Proliferation of Fibroblast-like Synoviocytes from The Patients with Rheumatoid Arthritis
  1. J.-M. Kim1,
  2. J. Bang2,
  3. Y.S. Kim3,
  4. H.-S. Kim4,
  5. S.-J. Hong5,
  6. S.-S. Kim6,
  7. H.-J. Jeong1,
  8. C.-N. Son1,
  9. S.-H. Kim1
  1. 1Division of Rheumatology, Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine
  2. 2Keimyung University Graduate School of Medicine, Daegu
  3. 3Division of Rheumatology, Department of Internal Medicine, Chosun University Hospital, Gwangju
  4. 4Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital
  5. 5Division of Rheumatology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul
  6. 6Division of Rheumatology, Department of Internal Medicine, Ulsan University School of Medicine, GangNeung Asan Hospital, Gangwon-do, Korea, Republic Of


Background Interleukin-17A (IL-17A) plays a critical role in the pathogenesis of rheumatoid arthritis (RA), which is characterized by exaggerated synovial proliferation. Autophagy is required to prevent accumulation of cellular damage and to ensure cellular homeostasis. Dysregulated autophagy has been reported to be involved in the pathogenesis of several diseases such as cancer and infections. Here, we hypothesized that IL-17A, a key cytokine in the development of RA, might have an impact on autophagic flux and that aberrant autophagy might be involved in expansion of synovial fibroblasts in the patients with RA, which is stimulated by pro-inflammatory cytokines.

Objectives 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) during total knee replacement surgery. FLS was cultured with IL-17A, autophagy inducer or inhibitor. The expression of marker proteins for autophagic flux (LC3B, Beclin1, Atg5, p62) and the formation of autophagolysosome (LAMP1) were analyzed by western blot. 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. Bafilomycin was used for inhibiting autophagic flux.

Results The expression of autophagy markers (LC3B, Beclin1, Atg5) was increased in the synovium of the patients with RA than in that of the patients with OA. Autophagy was also enhanced in RA-FLS compared with OA-FLS. IL-17A upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. In particular, IL-17A-induced accumulation of p62 was prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by the inhibition of autophagy.

Conclusions This study reveals that IL-17A stimulates autophagic flux 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.

  1. Lin NY, Beyer C, Giessl A, et al. Autophagy regulates TNFα-mediated joint destruction in experimental arthritis. Ann Rheum Dis. 2013 May;72(5):761–8.

  2. Connor AM, Mahomed N, Gandhi R, et al. TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther. 2012 Mar 14;14(2):R62.

Disclosure of Interest None declared

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