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Dexamethasone inhibits interleukin-1β-induced matrix metalloproteinase-9 expression in cochlear cells
1Department of Otolaryngology, Keimyung University School of Medicine, Daegu, Korea.
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 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.
Conclusion:
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.
Insights
Interleukin-1β (IL-1β) upregulates matrix metalloproteinase-9 (MMP-9) in cochlear cells via the p38 MAPK pathway. Dexamethasone inhibits this IL-1β-induced MMP-9 expression, offering potential therapeutic insights.
Area of Science:
- Oto-inflammatory mechanisms
- Molecular biology of hearing loss
- Cytokine signaling in the cochlea
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a role in cochlear pathology.
- Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine implicated in inner ear inflammation.
- Understanding IL-1β's effects on MMP-9 is crucial for developing treatments for hearing loss.
Purpose of the Study:
- To investigate the impact of IL-1β on MMP-9 expression in cochlear cells.
- To determine if dexamethasone regulates IL-1β-induced MMP-9 expression.
- To elucidate the molecular and signaling pathways involved in this process.
Main Methods:
- Utilized HEI-OC1 cells, a cell line derived from the mouse inner ear.
- Administered IL-1β with and without dexamethasone, and specific MAPK inhibitors (SB203580, SP600125, PD98059).
- Measured MMP-9 mRNA levels via RT-PCR and MMP-9 activity using gelatin zymography.
Main Results:
- IL-1β significantly increased MMP-9 mRNA and activity in a dose- and time-dependent manner.
- Dexamethasone treatment effectively inhibited IL-1β-induced MMP-9 expression.
- The p38 MAPK signaling pathway was identified as the primary mediator of IL-1β-induced MMP-9 expression, while JNK and ERK pathways were not involved.
Conclusions:
- IL-1β induces MMP-9 expression in cochlear cells through the p38 MAPK pathway.
- Dexamethasone acts as an inhibitor of this IL-1β-mediated MMP-9 induction.
- These findings highlight a potential therapeutic target for inflammatory conditions affecting hearing.
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