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Interleukin-1β Up-Regulates Inducible Nitric Oxide by Way of Phosphoinositide 3-Kinase-Dependent in a Cochlear Cell Model

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Affiliated Author(s)
남성일
Alternative Author(s)
Nam, Sung Il
Journal Title
Laryngoscope
ISSN
0023-852X
Issued Date
2006
Keyword
Interleukin-1βiNOSNOPI3 Kcochlea
Abstract
Objective: To investigate the effect of interleukin (IL)-1β on inducible nitric oxide (iNOS) expression in cochlea and the molecular and signaling mechanisms involved. Materials and Methods: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1β. 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-1β 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-1β in HEI-OC1 cells. Results: Treatment of IL-1β resulted in a concentration-dependent increase of iNOS protein and mRNA and NO production. One nanogram per milliliter of IL-1β treatment for 4 to 8 hours was sufficient to highly induce iNOS. IL-1β 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-1β-induced expressions of iNOS protein and mRNA. However, inhibition of JNKs and ERKs by SP29004 and PD98059, respectively, had no effect on the IL-1β-induced iNOS expression. Conclusions: These results suggest that the pro-inflammatory cytokine IL-1β 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.
Department
Dept. of Otorhinolaryngology (이비인후과학)
Publisher
School of Medicine
Citation
Sung-Il Nam. (2006). Interleukin-1β Up-Regulates Inducible Nitric Oxide by Way of Phosphoinositide 3-Kinase-Dependent in a Cochlear Cell Model. Laryngoscope, 116(12), 2166–2170. doi: 10.1097/01.mlg.0000243202.92548.fa
Type
Article
ISSN
0023-852X
DOI
10.1097/01.mlg.0000243202.92548.fa
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36286
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학)
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