Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells

Immunology. 2002 May;106(1):38-45. doi: 10.1046/j.1365-2567.2002.01401.x.

Abstract

Toll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-alpha induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kappaB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Drosophila Proteins*
  • Gene Expression Regulation / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / immunology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Signal Transduction / immunology*
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation / immunology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Drosophila Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases