The Novel Synthetic Peptide AESIS-1 Exerts a Preventive Effect on Collagen-Induced Arthritis Mouse Model via STAT3 Suppression

International Journal of Molecular Sciences

SeungBeom Park¹  JeongMin Park¹  KyungEun Kim²  HyunJeong Park³  Jisun Song⁴  TaeSung Kim⁴  Daeho Cho⁵  Suwon Jeon⁵  Sunyoung Park⁶  MyunSoo Kim⁶  MinKyung Jung⁷ 

[1] Cent’l Res. Inst., Ilyang Pharm. Co., Ltd., Hagal-ro 136beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do 17096, Korea;Department of Cosmetic Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul 04310, Korea;Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul 07345, Korea;Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Anam-dong 5-ga, Seongbuk-gu, Seoul 02841, Korea;Institute of Convergence Science, Korea University, Anam-ro 145, Seongbuk-ku, Seoul 02841, Korea;Kine Sciences, 525, Seolleung-ro, Gangnam-gu, Seoul 06149, Korea;Nano-Bio Resources Center, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul 04310, Korea;

关键词: rheumatoid arthritis;    collagen-induced arthritis;    peptide;    socs3;    stat3;    th17 cells;   

DOI  :  10.3390/ijms21020378

来源: DOAJ

【 摘 要 】

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with systemic inflammation and results in the destruction of joints and cartilage. The pathogenesis of RA involves a complex inflammatory process resulting from the action of various proinflammatory cytokines and, therefore, many novel therapeutic agents to block cytokines or cytokine-mediated signaling have been developed. Here, we tested the preventive effects of a small peptide, AESIS-1, in a mouse model of collagen-induced arthritis (CIA) with the aim of identifying a novel safe and effective biological for treating RA. This novel peptide significantly suppressed the induction and development of CIA, resulting in the suppression of synovial inflammation and cartilage degradation in vivo. Moreover, AESIS-1 regulated JAK/STAT3-mediated gene expression in vitro. In particular, the gene with the most significant change in expression was suppressor of cytokine signaling 3 (Socs3), which was enhanced 8-fold. Expression of the STAT3-specific inhibitor, Socs3, was obviously enhanced dose-dependently by AESIS-1 at both the mRNA and protein levels, resulting in a significant reduction of STAT3 phosphorylation in splenocytes from severe CIA mice. This indicated that AESIS-1 regulated STAT3 activity by upregulation of SOCS3 expression. Furthermore, IL-17 expression and the frequency of Th17 cells were considerably decreased by AESIS-1 in vivo and in vitro. Collectively, our data suggest that the novel synthetic peptide AESIS-1 could be an effective therapeutic for treating RA via the downregulation of STAT3 signaling.

【 授权许可】

Unknown