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- Title
Interleukin-1beta up-regulates inducible nitric oxide by way of phosphoinositide 3-kinase-dependent in a cochlear cell model.
- Authors
Nam S; Nam, Sung-Il
- Abstract
<bold>Objective: </bold>To investigate the effect of interleukin (IL)-1beta on inducible nitric oxide (iNOS) expression in cochlea and the molecular and signaling mechanisms involved.<bold>Materials and Methods: </bold>House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1beta. Pharmacologic inhibitors such as PD98059 (an extracellular-regulated protein kinase [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinase [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinases [JNKs]) inhibitor), and LY294002 (an inhibitor of phosphoinositide 3-kinase [PI3 K]) were used to see the role of JNKs, ERKs, p38 MAPK, or PI3 K signaling pathway(s) in iNOS expression in response to IL-1beta in HEI-OC1 cells. Western blot and reverse-transcription polymerase chain reaction analyses were used to measure iNOS protein and mRNA expression, respectively. Luciferase assay was carried out to measure the transcription of iNOS by IL-1beta in HEI-OC1 cells.<bold>Results: </bold>Treatment of IL-1beta resulted in a concentration-dependent increase of iNOS protein and mRNA and NO production. One nanogram per milliliter of IL-1beta treatment for 4 to 8 hours was sufficient to highly induce iNOS. IL-1beta treatment also led to activation of JNKs, ERKs, and p70S6 K. Interestingly, pharmacologic inhibition of the PI3 K signaling pathway by LY294002 resulted in strong down-regulation of the IL-1beta-induced expressions of iNOS protein and mRNA. However, inhibition of JNKs and ERKs by SP29004 and PD98059, respectively, had no effect on the IL-1beta-induced iNOS expression.<bold>Conclusions: </bold>These results suggest that the pro-inflammatory cytokine IL-1beta strongly induces iNOS expression and NO production in HEI-OC1 cells, and the induction appears to be achieved by increased iNOS transcription and activation of PI3 K signaling pathway.
- Publication
Laryngoscope, 2006, Vol 116, Issue 12, p2166
- ISSN
0023-852X
- Publication type
journal article