Luteolin suppresses IL-1β-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW982
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Abstract
Matrix metalloproteinases (MMPs) play an important role in tissue degradation in rheumatoid
synovium and inflammatory cytokines are essential in the pathogenesis of rheumatoid
arthritis (RA). This study was conducted to evaluate the efficacy of luteolin in regulating
interleukin-1beta (IL-1beta)-induced production of MMPs (MMP-1 and -3) and cytokines
(tumor necrosis factor (TNF)-alpha and IL-6) in human synovial cell line, SW982. Treatment
with luteolin at 1 or 10 microM significantly (P<0.05) inhibited IL-1beta-induced
MMPs (MMP-1 and -3) and cytokines (TNF-alpha and IL-6) production when measured by
enzyme-linked immunosorbent assay (ELISA). The mitogen-activated protein kinases (MAPKs)
represent an attractive target for RA because they can regulate MMP and cytokine expression.
The effects of luteolin on the activation of MAPKs and transcription factors were
also examined in SW982 cells by ELISA. IL-1beta-induced JNK and p38 activation were
inhibited by luteolin. Moreover, IL-1beta-induced activator protein-1 (AP-1) and nuclear
factor-kappaB (NF-kappaB) activation were inhibited by luteolin. These results suggest
that luteolin reduces the production of MMPs and cytokines in SW982 cells by inhibiting
MAPKs (JNK and p38) and transcription factors (AP-1 and NF-kappaB).
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