Heat shock up-regulates expression of Toll-like receptor-2 and Toll-like receptor-4 in human monocytes via p38 kinase signal pathway

Immunology. 2005 Apr;114(4):522-30. doi: 10.1111/j.1365-2567.2004.02112.x.

Abstract

Summary Heat stress can alert innate immunity by inducing stress proteins such as heat-shock proteins (HSPs). However, it remains unclear whether heat stress affects the activation of antigen-presenting cell (APC) in response to pathogen-associated molecule patterns (PAMPs) by directly regulating pathogen recognition receptors (PRRs). As an important kind of PRRs, Toll-like receptors (TLRs) play critical roles in the activation of immune system. In this study, we demonstrated that heat shock up-regulated the expression of HSP70 as well as TLR2 and TLR4 in monocytes. The induction of TLRs was prior to that of HSP70, which suggesting the up-regulation of TLR2 and TLR4 might be independent of the induction of HSP70. Heat shock activated p38 kinase, extracellular signal-related kinase (ERK) and nuclear factor-kappa B (NF-kappaB) signal pathways in monocytes. Pretreatment with specific inhibitor of p38 kinase, but not those of ERK and NF-kappaB, inhibited heat shock-induced up-regulation of TLR2 and TLR4. This indicates that p38 pathway takes part in heat shock-induced up-regulation of TLR2 and TLR4. Heat shock also increased lipoteichoic acid- or lipopolysaccharide-induced interleukin-6 production by monocytes. These results suggest that the p38 kinase-mediated up-regulation of TLR2 and TLR4 might be involved in the enhanced response to PAMP in human monocytes induced by heat shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western / methods
  • Cell Line
  • Flow Cytometry
  • Gene Expression Regulation
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / analysis
  • Hot Temperature*
  • Humans
  • Interleukin-6 / immunology
  • Leukotriene A4 / pharmacology
  • Lipopolysaccharide Receptors / analysis
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • NF-kappa B / metabolism
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Interleukin-6
  • Leukotriene A4
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • p38 Mitogen-Activated Protein Kinases