Flavopiridol inhibits lipopolysaccharide-induced TNF-α production through inactivation of nuclear factor-κB and mitogen-activated protein kinases in the MyD88-dependent pathway

Abedul Haque, Naoki Koide, Imtiaz Iftakhar-E-Khuda, Abu Shadat Mohammod Noman, Erdenezaya Odkhuu, Battuvshin Badamtseren, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)160-167
Number of pages8
JournalMICROBIOLOGY and IMMUNOLOGY
Volume55
Issue number3
DOIs
Publication statusPublished - 03-2011

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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