Open AccessInhibition of extracellular signal‐regulated kinase 1/2 augments nitric oxide production in lipopolysaccharide‐stimulated RAW264.7 macrophage cells
Author(s) -
Koide Naoki,
Ito Hiroyasu,
Mu Mya Mya,
Sugiyama Tsuyoshi,
Hassan Ferdaus,
Islam Shamima,
Mori Isamu,
Yoshida Tomoaki,
Yokochi Takashi
Publication year - 2005
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1016/j.femsim.2005.03.012
Subject(s) - kinase , nitric oxide , biology , mapk/erk pathway , lipopolysaccharide , p38 mitogen activated protein kinases , protein kinase a , mitogen activated protein kinase 3 , microbiology and biotechnology , extracellular , mitogen activated protein kinase , tyrosine kinase , nitric oxide synthase , signal transduction , biochemistry , endocrinology
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.