TY - JOUR
T1 - Therapeutic effect of erythroid differentiation regulator 1 (Erdr1) on collagen-induced arthritis in DBA/1J mouse
AU - Kim, Kyung Eun
AU - Kim, Sungryung
AU - Park, Sunyoung
AU - Houh, Younkyung
AU - Yang, Yoolhee
AU - Park, Seung Beom
AU - Kim, Sangyoon
AU - Kim, Daejin
AU - Hur, Dae Young
AU - Kim, Seonghan
AU - Park, Hyun Jeong
AU - Bang, Sa Ik
AU - Cho, Daeho
PY - 2016
Y1 - 2016
N2 - 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, collageninduced 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.
AB - 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, collageninduced 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.
KW - Erythroid differentiation regulator 1 (Erdr1)
KW - Immune response
KW - Immunity
KW - Immunology and Microbiology Section
KW - Inflammation
KW - Interleukin-18 (IL-18)
KW - Rheumatoid arthritis
KW - Synovial fibroblast migration
UR - http://www.scopus.com/inward/record.url?scp=84998773606&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13047
DO - 10.18632/oncotarget.13047
M3 - Article
C2 - 27823968
AN - SCOPUS:84998773606
SN - 1949-2553
VL - 7
SP - 76354
EP - 76361
JO - Oncotarget
JF - Oncotarget
IS - 47
ER -