Research Perspective: Immunology:
Therapeutic effect of erythroid differentiation regulator 1 (Erdr1) on collagen-induced arthritis in DBA/1J mouse
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Abstract
Kyung Eun Kim1,2, Sungryung Kim2, Sunyoung Park2, Younkyung Houh2, Yoolhee Yang3, Seung Beom Park4, Sangyoon Kim4, Daejin Kim5, Dae Young Hur5, Seonghan Kim5, Hyun Jeong Park6,*, Sa Ik Bang3,* and Daeho Cho1,2,*
1 Department of Cosmetic Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea
2 Department of Biological Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea
3 Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Republic of Korea
4 Biotech. Team, Cent’l Res. Inst. Ilyang Pharm. Co., Ltd., Gyeonggi-do, Republic of Korea
5 Department of Anatomy, Inje University College of Medicine, Busan, Republic of Korea
6 Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
* These authors have contributed equally to this work
Correspondence to:
Daeho Cho, email:
Sa Ik Bang, email:
Hyun Jeong Park, email:
Keywords: erythroid differentiation regulator 1 (Erdr1), rheumatoid arthritis, inflammation, interleukin-18 (IL-18), synovial fibroblast migration, Immunology and Microbiology Section, Immune response, Immunity
Received: August 25, 2016 Accepted: October 28, 2016 Published: November 03, 2016
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r)Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.
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