Background/Purpose: Here, we assumed that intracellular autophagy mechanism and its protein microtubule-associated protein 1 light chain-3B (LC3B) play an important role in the synovial fibroblasts of rheumatoid arthritis, and identified it through TNF-ɑ stimulated synovial fibroblasts and animal model of rheumatoid arthritis.

Methods: Mice deficient in microtubule associated protein-1 light chain-3B (LC3B-/-) were induced arthritis by the injection of type II collagen antibody and LPS. The clinical and histologic scores of arthritis and pro-inflammatory cytokines were measured from arthritic mice. Human synovial fibroblasts were obtained from the patients with rheumatoid arthritis. Their autophagic induction and its mechanisms were measured by western blots and ELISA assays after TNF-ɑ treatment.

Results: In the results, we found that the clinical and histologic scores of arthritis and pro-inflammatory cytokines such as TNF-ɑ, IL-1β and IL-6 in joint tissues were significantly decreased in the LC3B-/- arthritic mice compared to wild type littermates. We also identified that autophagy proteins like LC3B were expressed in synovial fibroblasts stimulated with TNF-ɑ, and in this process, the activation of Jun-N terminal kinase (JNK) through reactive oxygen species (ROS) generated by a TNF-ɑ and the expression of early growth response protein-1 (Egr-1) were important to LC3B expression. After knock down of LC3B by siRNA in the TNF-ɑ stimulated synovial fibroblasts, the proliferation, migration and invasion capacities of these cells were significantly reduced and these phenomenons were associated with the decrease of cyclin D1 and vimentin by the increased ROS after autophagy inhibition.

Conclusion: In conclusion, we confirmed that autophagic protein LC3B induced by TNF-ɑ plays an important role in the joint inflammation and destruction of rheumatoid arthritis and suggest this protein as a new therapeutic target in the treatment of rheumatoid arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autophagy-protein-microtubule-associated-protein-1-light-chain-3b-lc3b-regulates-joint-inflammation-and-destruction-in-rheumatoid-arthritis/