title: Dexamethasone inhibits interleukin-1β-induced matrix metalloproteinase-9 expression in cochlear cells.
abstract: OBJECTIVE
  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 involved.
  
  
  METHODS
  House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1β 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-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, significantly 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.
  
  
  CONCLUSIONS
  These results suggest that the pro-inflammatory cytokine IL-1β strongly induces MMP-9 expression via activation of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.
authors.affiliation: Department of Otolaryngology, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Nam
authors.affiliation: Department of Immunology, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Taeg-Kyu
authors.initials: TK
authors.lastname: Kwon
keywords: Cochlea; Interleukin-1beta; Matrix metalloproteinase 9; p38 Mitogen-activated protein kinases