Immune Netw.  2005 Mar;5(1):30-35. 10.4110/in.2005.5.1.30.

p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinase Regulate Nitric Oxide Production and Inflammatory Cytokine Expression in Raw Cells

• Choi CH
• Kim SH

• KMID: 2150587
• DOI: http://doi.org/10.4110/in.2005.5.1.30

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.

Keyword

p38; ERK; nitric oxide; cytokine; LPS; ROS

MeSH Terms

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
Interleukin-12
Interleukin-6
Nitric Oxide
Nitric Oxide Synthase Type II
Phosphotransferases
Protein Kinases
RNA, Messenger
Reactive Oxygen Species
Tumor Necrosis Factor-alpha