Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB

Cell Signal. 2005 Mar;17(3):385-94. doi: 10.1016/j.cellsig.2004.08.005.

Abstract

Protein kinase C (PKC)alpha/beta dependent signaling events downstream of TLR4 or TLR2 were investigated in neutrophils stimulated with LPS or PGN. Pretreatment of neutrophils with the structurally distinct PKCalpha/beta inhibitors Go6976 or GF109203X decreased nuclear translocation of NF-kappaB and production of the proinflammatory cytokine TNF-alpha. Inhibition of PKCalpha/beta also prevented LPS or PGN induced phosphorylation of IKKalpha/beta, phosphorylation and degradation of IkappaB-alpha, as well as phosphorylation of the p65 subunit of NF-kappaB. Activation of p38, JNK, and ERK 1/2 in response to TLR2 engagement was diminished in neutrophils in which PKCalpha/beta was inhibited. However, no alteration in the activation of these kinases was found in TLR4 stimulated neutrophils when PKCalpha/beta was blocked. Such results indicate that distinct intracellular signalling pathways leading to MAPK activation are induced by TLR4 and TLR2 stimulation. PKCalpha/beta can regulate NF-kappaB dependent transcription in neutrophils both by enhancing nuclear translocation of NF-kappaB and also by stimulating phosphorylation of the p65 subunit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Enzyme Activation
  • I-kappa B Kinase
  • In Vitro Techniques
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism*
  • Neutrophil Activation
  • Neutrophils / metabolism*
  • Peptidoglycan / pharmacology
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Transport
  • Receptors, Immunologic / physiology*
  • Signal Transduction
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Peptidoglycan
  • Receptors, Immunologic
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Protein Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Mitogen-Activated Protein Kinases