Dexamethasone Inhibits Interleukin-1β-Induced Matrix Metalloproteinase-9 Expression in Cochlear Cells
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Objectives. To investigate the effect of interleukin (IL)-1β on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1β-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms in- volved. Methods. House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1β with/without dexametha- sone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracel- lular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibi- tor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1β-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-1β-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1β (1 ng/mL)- induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, signifi- cantly inhibited IL-1β-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1β-induced MMP-9 expression. Conclusion. These results suggest that the pro-inflammatory cytokine IL-1β strongly induces MMP-9 expression via activa- tion of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.
Abstract
Objectives. To investigate the effect of interleukin (IL)-1β on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1β-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms in- volved. Methods. House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1β with/without dexametha- sone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracel- lular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibi- tor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1β-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-1β-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1β (1 ng/mL)- induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, signifi- cantly inhibited IL-1β-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1β-induced MMP-9 expression. Conclusion. These results suggest that the pro-inflammatory cytokine IL-1β strongly induces MMP-9 expression via activa- tion of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.
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