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

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-α, IL-1β, 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-1β and IL-6. SB203580 increased LPS-induced expression of TNF-α 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-1β and IL-6. p38 signaling pathways are involved in LPS-induced TNF-α and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

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