Hepatocyte toll-like receptor 2 expression in vivo and in vitro: role of cytokines in induction of rat TLR2 gene expression by lipopolysaccharide.
We and others have demonstrated previously that cytokines, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNFalpha), regulate LPS recognition proteins such as CD14 in the liver and on hepatocytes. Based on recent findings that the mammalian homologue of Drosophila Toll participates in LPS signaling, we examined the regulation of Toll-Like Receptor (TLR) gene expression by cytokines in vitro and its distribution in vivo with a focus on the liver as a site of host-microbe interaction. Our results show that IL-1beta and/or TNFalpha participate in the upregulation of TLR2 mRNA levels in hepatocytes. Rats treated concurrently with LPS and antagonists of the IL-1 or TNFalpha receptor demonstrated significantly reduced LPS-induced hepatic expression of TLR2 compared to animals treated with LPS alone. The increase in hepatic TLR2 mRNA expression was associated with enhanced transcription as determined by nuclear run-on analysis. LPS treatment in vivo caused a marked TLR2 mRNA up-regulation in all of the tissues examined, with liver showing the highest expression. The high level of TLR2 expression in the liver may have important implications for pathogen-host interactions or microbial signaling.
Liu
S
S
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Salyapongse
A N
AN
Geller
D A
DA
Vodovotz
Y
Y
Billiar
T R
TR
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D029721:Drosophila Proteins; D019446:Endotoxemia / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
D016207:Cytokines; D029721:Drosophila Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha