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

J Leukoc Biol. 2004 Jun;75(6):1056-61. doi: 10.1189/jlb.0104108. Epub 2004 Mar 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins / genetics
  • Down-Regulation*
  • Female
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-1 Type I
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Amyloid A Protein / genetics
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Transforming Growth Factor beta / pharmacology*


  • Apolipoproteins
  • Interleukin-1
  • Membrane Glycoproteins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Serum Amyloid A Protein
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Transforming Growth Factor beta