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A Toll‐like receptor 2 ligand, P am3 CSK 4, augments interferon‐γ‐induced nitric oxide production via a physical association between MyD88 and interferon‐γ receptor in vascular endothelial cells
Author(s) -
Tsolmongyn Bilegtsaikhan,
Koide Naoki,
Jambalganiin Ulziisaikhan,
Odkhuu Erdenezaya,
Naiki Yoshikazu,
Komatsu Takayuki,
Yoshida Tomoaki,
Yokochi Takashi
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12147
Subject(s) - phosphorylation , tyrosine phosphorylation , stat1 , microbiology and biotechnology , stat protein , signal transduction , nitric oxide synthase , receptor , chemistry , biology , cancer research , stat3 , nitric oxide , endocrinology , biochemistry
Summary The effect of Pam3CSK4, a Toll‐like receptor 2 ( TLR 2) ligand, on interferon‐γ ( IFN ‐γ) ‐induced nitric oxide ( NO ) production in mouse vascular endothelial END‐D cells was studied. Pre‐treatment or post‐treatment with Pam3CSK4 augmented IFN ‐γ‐induced NO production via enhanced expression of an inducible NO synthase ( iNOS ) protein and mRNA . Pam3CSK4 augmented phosphorylation of Janus kinase 1 and 2, followed by enhanced phosphorylation of signal transducer and activator of transcription 1 ( STAT 1) at tyrosine 701. Subsequently, the enhanced STAT1 activation augmented IFN ‐γ‐induced IFN‐regulatory factor 1 expression leading to the iNOS expression. Pam3CSK4 also induced the activation of p38 and subsequent phosphorylation of STAT 1 at serine 727. A pharmacological p38 inhibitor abolished the augmentation of IFN‐γ‐induced NO production by Pam3CSK4. Surprisingly, Pam3CSK4 enhanced a physical association of MyD88 and IFN ‐γ receptor. Together, these findings suggest that Pam3CSK4 up‐regulates IFN ‐γ signalling in vascular endothelial cells via the physical association between MyD88 and IFN ‐γ receptor α, and p38‐dependent serine 727 STAT 1 phosphorylation.