Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3
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Chitinase-3-like 1 (CHI3L1) is a key factor in regulating inflammatory processes and development of rheumatoid arthritis (RA) since is highly produced by synoviocytes and macrophages in the development RA. Collagen-induced arthritis (CIA) model is the most widely used because its pathogenesis is similar to human RA. Thus, we aimed to investigate if anti-CHI3L1 antibody could reduce RA development in the CIA model. To induce CIA, DBA1/J mice were immunized with a type II bovine collagen emulsion in complete Freund’s adjuvant, and boosted type II bovine collagen. THP-1 and MH7A cells were used for pro-inflammation responses. Anti-CHI3L1 Ab treatment reduced the RA clinical score and paw thickness of mice. Inflammation-induced matrix metalloproteinase 3 (MMP3) expression was reduced by inhibiting CHI3L1, and MMP3 knockdown suppressed the expression of RA-related inflammatory cytokines in LPS-treated THP-1 and MH7A cells. Our findings suggest that anti-CHI3L1 Ab showed significant anti-arthritic effects by inhibiting MMP3 expression.
Abstract
Chitinase-3-like 1 (CHI3L1) is a key factor in regulating inflammatory processes and development of rheumatoid arthritis (RA) since is highly produced by synoviocytes and macrophages in the development RA. Collagen-induced arthritis (CIA) model is the most widely used because its pathogenesis is similar to human RA. Thus, we aimed to investigate if anti-CHI3L1 antibody could reduce RA development in the CIA model. To induce CIA, DBA1/J mice were immunized with a type II bovine collagen emulsion in complete Freund’s adjuvant, and boosted type II bovine collagen. THP-1 and MH7A cells were used for pro-inflammation responses. Anti-CHI3L1 Ab treatment reduced the RA clinical score and paw thickness of mice. Inflammation-induced matrix metalloproteinase 3 (MMP3) expression was reduced by inhibiting CHI3L1, and MMP3 knockdown suppressed the expression of RA-related inflammatory cytokines in LPS-treated THP-1 and MH7A cells. Our findings suggest that anti-CHI3L1 Ab showed significant anti-arthritic effects by inhibiting MMP3 expression.