Inhibition of extracellular signal-regulated kinase 1/2 augments nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells

Naoki Koide, Hiroyasu Ito, Mya Mu Mya, Tsuyoshi Sugiyama, Ferdaus Hassan, Shamima Islam, Isamu Mori, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The present study was conducted to determine effects of U0126, a specific inhibitor of mitogen-activated kinase kinase 1/2, on production of nitric oxide (NO) in RAW264.7 macrophage cells. U0126 significantly enhanced NO production in lipopolysaccharide (LPS) but not CpG DNA or interferon-γ-stimulated RAW264.7 cells. In contrast, U0124, a negative control for U0126, did not affect LPS-induced NO production. Further, a series of inhibitors of p38, phosphatidyl-inositol 3-kinase and Janus tyrosine kinase rather caused suppression in LPS-stimulated RAW264.7 cells. U0126 was found to definitely inhibit phosphorylation of extracellular signal-regulated kinase (Erk) 1/2 and augment the levels of inducible type of NO synthase. Antisense oligonucleotides of Erk1/2 also augmented LPS-induced NO production. Inactivation of Erk1/2 by U0126 furthermore inhibited LPS-induced activating protein-1 activation, but not nuclear factor-κB activation. The results suggest that Erk1/2 might negatively regulate NO production in LPS-stimulated RAW264.7 cells.

Original languageEnglish
Pages (from-to)213-219
Number of pages7
JournalFEMS Immunology and Medical Microbiology
Volume45
Issue number2
DOIs
Publication statusPublished - 01-08-2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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