Gene interactions and pathways from curated databases and text-mining
J Leukoc Biol 2004, PMID: 15039464

TGF-beta down-regulates IL-1alpha-induced TLR2 expression in murine hepatocytes.

Matsumura, Takayuki; Hayashi, Hidetoshi; Takii, Takemasa; Thorn, Caroline F; Whitehead, Alexander S; Inoue, Jun-Ichiro; Onozaki, Kikuo

We have previously reported that the proinflammatory cytokine interleukin (IL)-1alpha can up-regulate functional Toll-like receptor 2 (TLR2) expression in primary-cultured murine hepatocytes, and bacterial lipopeptide (BLP) is capable of signaling through TLR2 to induce serum amyloid A (SAA) expression in hepatocytes. In the present study, we investigated the effect of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta) on TLR2 expression in primary-cultured murine hepatocytes. At the mRNA and protein levels, TGF-beta up-regulated TLR2 expression but inhibited TLR2 expression induced by IL-1alpha at 24 h. BLP-induced SAA promoter activity could be augmented by pretreatment with IL-1alpha but not TGF-beta or the combination of TGF-beta and IL-1alpha. TLR2 promoter activity and nuclear factor (NF)-kappaB activation by IL-1alpha were inhibited by TGF-beta treatment. Pretreatment with TGF-beta strongly suppressed IL-1alpha-induced TLR2 promoter activity and NF-kappaB activation, which was consistent with the down-regulation of type I IL-1 receptor (IL-1RI) mRNA expression. IL-1alpha up-regulated IL-1RI mRNA, but it was inhibited by the treatment with TGF-beta. These results suggest that TGF-beta suppresses the induction of TLR2 expression by IL-1alpha through down-regulation of IL-1RI expression. These results also demonstrate the disparity between IL-1alpha and TGF-beta in regulating TLR2-mediated SAA production in hepatocytes.

Document information provided by NCBI PubMed

Text Mining Data

TLR2 → IL-1alpha: " TGF-beta down-regulates IL-1alpha induced TLR2 expression in murine hepatocytes "

SAA → BLP: " At the mRNA and protein levels, TGF-beta up-regulated TLR2 expression but inhibited TLR2 expression induced by IL-1alpha at 24 h. BLP induced SAA promoter activity could be augmented by pretreatment with IL-1alpha but not TGF-beta or the combination of TGF-beta and IL-1alpha "

TLR2 → IL-1alpha: " At the mRNA and protein levels, TGF-beta up-regulated TLR2 expression but inhibited TLR2 expression induced by IL-1alpha at 24 h. BLP induced SAA promoter activity could be augmented by pretreatment with IL-1alpha but not TGF-beta or the combination of TGF-beta and IL-1alpha "

nuclear factor (NF)-kappaB → IL-1alpha: " TLR2 promoter activity and nuclear factor (NF)-kappaB activation by IL-1alpha were inhibited by TGF-beta treatment "

TLR2 → IL-1alpha: " Pretreatment with TGF-beta strongly suppressed IL-1alpha induced TLR2 promoter activity and NF-kappaB activation, which was consistent with the down-regulation of type I IL-1 receptor ( IL-1RI ) mRNA expression "

NF-kappaB → IL-1alpha: " Pretreatment with TGF-beta strongly suppressed IL-1alpha induced TLR2 promoter activity and NF-kappaB activation, which was consistent with the down-regulation of type I IL-1 receptor ( IL-1RI ) mRNA expression "

TLR2 → IL-1alpha: " These results suggest that TGF-beta suppresses the induction of TLR2 expression by IL-1alpha through down-regulation of IL-1RI expression "

SAA → TLR2: " These results also demonstrate the disparity between IL-1alpha and TGF-beta in regulating TLR2 mediated SAA production in hepatocytes "

Manually curated Databases

No curated data.