TY - JOUR
T1 - Inhibition of extracellular signal-regulated kinase 1/2 augments nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells
AU - Koide, Naoki
AU - Ito, Hiroyasu
AU - Mya, Mya Mu
AU - Sugiyama, Tsuyoshi
AU - Hassan, Ferdaus
AU - Islam, Shamima
AU - Mori, Isamu
AU - Yoshida, Tomoaki
AU - Yokochi, Takashi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research (Kakenhi:15790229) from the Ministry of Education, Science, Sports and Culture of Japan. We are grateful to K. Takahashi for the expert technical assistance.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.femsim.2005.03.012
DO - 10.1016/j.femsim.2005.03.012
M3 - Article
C2 - 16051071
AN - SCOPUS:22844436330
VL - 45
SP - 213
EP - 219
JO - Pathogens and Disease
JF - Pathogens and Disease
SN - 2049-632X
IS - 2
ER -