Heat shock up-regulates expression of Toll-like receptor-2 and Toll-like receptor-4 in human monocytes via p38 kinase signal pathway.
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.
Zhou
Jun
J
Institute of Immunology, Zhejiang University, Hangzhou, People's Republic of China.
An
Huazhang
H
Xu
Hongmei
H
Liu
Shuxun
S
Cao
Xuetao
X
D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D017572:Leukotriene A4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D015850:Interleukin-6; D017572:Leukotriene A4; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases