| RRC ID |
45206
|
| Author |
Tsolmongyn B, Koide N, Jambalganiin U, Odkhuu E, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
|
| Title |
A Toll-like receptor 2 ligand, Pam3CSK4, augments interferon-γ-induced nitric oxide production via a physical association between MyD88 and interferon-γ receptor in vascular endothelial cells.
|
| Journal |
Immunology
|
| Abstract |
The effect of Pam3CSK4, a Toll-like receptor 2 (TLR2) 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 (STAT1) 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 STAT1 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 STAT1 phosphorylation.
|
| Volume |
140(3)
|
| Pages |
352-61
|
| Published |
2013-11-1
|
| DOI |
10.1111/imm.12147
|
| PMID |
23826757
|
| PMC |
PMC3800440
|
| MeSH |
Animals
Cell Line
Endothelium, Vascular / drug effects*
Endothelium, Vascular / immunology
Gene Expression Regulation / drug effects
Interferon gamma Receptor
Interferon-Stimulated Gene Factor 3 / metabolism
Interferon-gamma / immunology
Lipopeptides / pharmacology*
MAP Kinase Kinase 4 / metabolism
MAP Kinase Signaling System / drug effects
Mice
Myeloid Differentiation Factor 88 / metabolism*
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / genetics
Nitric Oxide Synthase Type II / metabolism*
Phosphorylation / drug effects
Protein Binding
Receptors, Interferon / metabolism*
Toll-Like Receptor 2 / agonists*
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
3.231
|
| Times Cited |
12
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
