Bacterial Lipopolysaccharide Induces Transforming Growth Factor β and Hepatocyte Growth Factor through Tolllike Receptor 2 in Cultured Human Colon Cancer Cells

Abstract

This study examined, in human cancer lines, the pattern of cytokine production stimulated by lipopolysaccharide (LPS), a major component of outer surface of gram-negative bacteria, and characterized the expression pattern of CD14, cell surface LPS receptor antigen, and toll-like receptors (TLRs), which appear to be key regulators of the innate immune response system. Two colon cancer cell lines (DLD and LoVo), a hepatocellular carcinoma cell line and a myelomonocytic cell line were incubated with LPS for 0-72 h, and transforming growth factor (TGF) beta1 and beta2, hepatocyte growth factor (HGF) and interleukins 6, 8 and 15 were assayed. The only changes induced by incubation with LPS were significant increases in TGFbeta1 production at 12 h, and in HGF production at 72 h, in LPS-stimulated DLD cells, and significant increases in TGFbeta2 production after 12 h and in HGF after 72 h in LoVo cells. Using reverse transcriptase-polymerase chain reaction analysis, expression of CD14 and TLR-2 mRNA was detected in DLD and LoVo cells, and expression of TLR-4 mRNA was detected in PLC/PRF/5 and KG-1 cells. These results suggest that LPS induces TGFbeta and HGF production mediated by CD14/TLR-2 in cultured human colon cancer cell lines.