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

被引:6
作者
Kim, Kyung Eun [1 ,2 ]
Jeon, Suwon [3 ]
Song, Jisun [4 ]
Kim, Tae Sung [4 ]
Jung, Min Kyung [2 ]
Kim, Myun Soo [5 ]
Park, Sunyoung [5 ]
Park, Seung Beom [6 ]
Park, Jeong Min [6 ]
Park, Hyun Jeong [7 ]
Cho, Daeho [3 ,5 ]
机构
[1] Sookmyung Womens Univ, Dept Cosmet Sci, Chungpa Dong 2 Ka, Seoul 04310, South Korea
[2] Sookmyung Womens Univ, Nano Bio Resources Ctr, Chungpa Dong 2 Ka, Seoul 04310, South Korea
[3] Korea Univ, Inst Convergence Sci, Anam Ro 145, Seoul 02841, South Korea
[4] Korea Univ, Coll Life Sci & Biotechnol, Dept Life Sci, Anam Dong 5 Ga, Seoul 02841, South Korea
[5] Kine Sci, 525 Seolleung Ro, Seoul 06149, South Korea
[6] Ilyang Pharm Co Ltd, Centl Res Inst, Hagal Ro 136beon Gil, Yongin 17096, Gyeonggi Do, South Korea
[7] Catholic Univ Korea, Yeouido St Marys Hosp, Dept Dermatol, Seoul 07345, South Korea
基金
新加坡国家研究基金会;
关键词
rheumatoid arthritis; collagen-induced arthritis; peptide; SOCS3; STAT3; Th17; cells; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; JAK INHIBITORS; FUTURE; INFLAMMATION; PATHWAYS; IL-6; DIFFERENTIATION; RECOMMENDATIONS; INTERLEUKIN-6;
D O I
10.3390/ijms21020378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
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页数:17
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