The novel synthetic peptide AESIS-1 exerts a preventive effect on collagen-induced arthritis mouse model via STAT3 suppression

Kyung Eun Kim, Suwon Jeon, Jisun Song, Tae Sung Kim, Min Kyung Jung, Myun Soo Kim, Sunyoung Park, Seung Beom Park, Jeong Min Park, Hyun Jeong Park, Daeho Cho

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number378
JournalInternational journal of molecular sciences
Volume21
Issue number2
DOIs
Publication statusPublished - 2020 Jan 2

Keywords

  • Collagen-induced arthritis
  • Peptide
  • Rheumatoid arthritis
  • SOCS3
  • STAT3
  • Th17 cells

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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