RRC ID |
18179
|
Author |
Haque A, Koide N, Iftakhar-E-Khuda I, Noman AS, Odkhuu E, Badamtseren B, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
|
Title |
Flavopiridol inhibits lipopolysaccharide-induced TNF-α production through inactivation of nuclear factor-κB and mitogen-activated protein kinases in the MyD88-dependent pathway.
|
Journal |
Microbiol Immunol
|
Abstract |
Flavopiridol is a cyclin-dependent kinase inhibitor and inhibits the growth of various cancer cells. The effect of flavopiridol on lipopolysaccharide (LPS)-induced proinflammatory mediator production was examined in RAW 264.7 macrophage-like cells. Flavopiridol significantly reduced the production of tumor necrosis factor-α and, to a lesser extent, nitric oxide in LPS-stimulated cells. Flavopiridol inhibited the activation of nuclear factor-κB and IκB kinase in response to LPS. Flavopiridol also inhibited the activation of a series of mitogen-activated protein kinases, such as p38, stress-activated protein kinase/c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 in response to LPS. However, flavopiridol did not alter the expression of tumor necrosis factor receptor-associated factor 6, myeloid differentiation factor 88 (MyD88) or CD14/toll-like receptor (TLR) 4. Flavopiridol inhibited nitric oxide production induced by a MyD88-dependent TLR2 ligand, but not a MyD88-independent TLR3 ligand. Further, flavopiridol did not alter the phosphorylation of interferon regulatory factor 3 in the MyD88-independent pathway. Therefore, it was suggested that flavopiridol exclusively inhibited the activation of nuclear factor-κB and mitogen-activated protein kinases in the MyD88-dependent pathway. Flavopiridol might be useful for the prevention of LPS-induced inflammatory response.
|
Volume |
55(3)
|
Pages |
160-7
|
Published |
2011-3-1
|
DOI |
10.1111/j.1348-0421.2010.00304.x
|
PMID |
21204955
|
MeSH |
Animals
Cell Line
Flavonoids / pharmacology*
Gene Expression Regulation, Archaeal / drug effects*
Lipopolysaccharide Receptors / metabolism
Lipopolysaccharides / metabolism*
Macrophages / drug effects
Mice
Mitogen-Activated Protein Kinases / metabolism*
Myeloid Differentiation Factor 88 / metabolism*
NF-kappa B / metabolism*
Nitric Oxide / biosynthesis
Phosphorylation / drug effects
Piperidines / pharmacology*
Protein Kinase Inhibitors / pharmacology*
Signal Transduction / drug effects
TNF Receptor-Associated Factor 6 / metabolism
Toll-Like Receptors / metabolism
Tumor Necrosis Factor-alpha / biosynthesis*
|
IF |
1.566
|
Times Cited |
8
|
WOS Category
|
MICROBIOLOGY
IMMUNOLOGY
|
Resource |
Human and Animal Cells |
RAW 264(RCB0535) |