Lipopolysaccharide enhances interferon-gamma-induced nitric oxide (NO) production in murine vascular endothelial cells via augmentation of interferon regulatory factor-1 activation.
Lipopolysaccharide (LPS) enhances the production of nitric oxide (NO) in interferon (IFN)-gamma-stimulated vascular endothelial cells. We studied the mechanism by which LPS enhances IFN-gamma-induced NO production by using the murine vascular endothelial cell line, END-D. LPS enhanced IFN-gamma-induced NO production via augmented expression of inducible type NO synthase (iNOS) mRNA. LPS significantly augmented the activation of interferon regulatory factor (IRF)-1 in IFN-gamma-stimulated END-D cells, although it did not affect the activation of either MyD88-dependent nuclear factor (NF)-kappaB or MyD88-independent IRF-3. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), prevented the nuclear translocation of IRF-1 in LPS and IFN-gamma-stimulated END-D cells, and inhibited the iNOS expression and NO production in those cells. Therefore, it is proposed that LPS enhanced NO production in IFN-gamma-stimulated END-D cells via augmenting p38 MAPKmediated IRF-1 activation.
Koide
Naoki
N
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. koide@aichi-med-u.ac.jp
Mu
Mya Mya
MM
Hassan
Ferdaus
F
Islam
Shamima
S
Tumurkhuu
Gantsetseg
G
Dagvadorj
Jargalsaikhan
J
Naiki
Yoshikazu
Y
Mori
Isamu
I
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D000818:Animals; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D017930:Genes, Reporter; D007150:Immunohistochemistry; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D050856:Interferon Regulatory Factor-1; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II