Dexamethasone Inhibits Interleukin-1beta-Induced Matrix Metalloproteinase-9 Expression in Cochlear Cells

ABSTRACT

OBJECTIVES: To investigate the effect of interleukin (IL)-1beta on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1beta-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms involved. METHODS: House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1beta with/without dexamethasone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracellular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1beta-induced MMP-9 expression in HEI-OC1 cells. Reverse transcription-polymerase chain reaction and gelatin zymography were used to measure mRNA expression level of MMP-9 and activity of MMP-9, respectively. RESULTS: Treatment with IL-1beta-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1beta (1 ng/mL)-induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, significantly inhibited IL-1beta-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1beta-induced MMP-9 expression. CONCLUSION: These results suggest that the pro-inflammatory cytokine IL-1beta strongly induces MMP-9 expression via activation of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.