TGF-β down-regulates IL-1α-induced TLR2 expression in murine hepatocytes.

We have previously reported that the proinflammatory cytokine interleukin (IL)-1α 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-β (TGF-β) on TLR2 expression in primary-cultured murine hepatocytes. At the mRNA and protein levels, TGF-β up-regulated TLR2 expression but inhibited TLR2 expression induced by IL-1α at 24 h. BLP-induced SAA promoter activity could be augmented by pretreatment with IL-1α but not TGF-β or the combination of TGF-β and IL-1α. TLR2 promoter activity and nuclear factor (NF)-κB activation by IL-1α were inhibited by TGF-β treatment. Pretreatment with TGF-β strongly suppressed IL-1α-induced TLR2 promoter activity and NF-κB activation, which was consistent with the down-regulation of type I IL-1 receptor (IL-1RI) mRNA expression. IL-1α up-regulated IL-1RI mRNA, but it was inhibited by the treatment with TGF-β. These results suggest that TGF-β suppresses the induction of TLR2 expression by IL-1α through down-regulation of IL-1RI expression. These results also demonstrate the disparity between IL-1α and TGF-β in regulating TLR2-mediated SAA production in hepatocytes.