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 interl eukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), regulate LPS re cognition proteins such as CD14 in the liver and on hepatocytes. Based on r ecent findings that the mammalian homologue of Drosophila Toll participates in LPS signaling, we examined the regulation of Toll-Like Receptor (TLR) g ene expression by cytokines in vitro and its distribution in vivo with a fo cus on the liver as a site of host-microbe interaction. Our results show th at IL-1 beta and/or TNF alpha participate in the upregulation of TLR2 mRNA levels in hepatocytes. Rats treated concurrently with LPS and antagonists o f the IL-1 or TNF alpha receptor demonstrated significantly reduced LPS-ind uced 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 vi vo caused a marked TLR2 mRNA up-regulation in all of the tissues examined, with liver showing the highest expression. The high level of TLR2 expressio n in the liver may have important implications for pathogen-host interactio ns or microbial signaling.