p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinase Regulate Nitric Oxide Production and Inflammatory Cytokine Expression in Raw Cells.
- Author:
Cheol Hee CHOI
1
;
Sang Hyun KIM
Author Information
- Publication Type:Original Article
- Keywords: p38; ERK; nitric oxide; cytokine; LPS; ROS
- MeSH: Gene Expression; Interleukin-12; Interleukin-6; Macrophages; MAP Kinase Signaling System; Nitric Oxide Synthase Type II; Nitric Oxide*; Phosphotransferases*; Protein Kinases*; Reactive Oxygen Species; RNA, Messenger; Tumor Necrosis Factor-alpha
- From:Immune Network 2005;5(1):30-35
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. METHODS: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. RESULTS: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-alpha, IL-1beta, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS-induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-1beta and IL-6. SB203580 increased LPS-induced expression of TNF-alpha and IL-12, and reactive oxygen species production, but PD98059 had no effect. CONCLUSION: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-1beta and IL-6. p38 signaling pathways are involved in LPS-induced TNF-alpha and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.
