Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells

J Int Med Res. 2001 Sep-Oct;29(5):409-20. doi: 10.1177/147323000102900505.

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.

MeSH terms

  • Antigens, CD / genetics
  • Colonic Neoplasms
  • Cytokines / genetics
  • Drosophila Proteins*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gram-Negative Bacteria
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharides / pharmacology*
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / physiology*
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / genetics*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Cytokines
  • Drosophila Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transforming Growth Factor beta
  • Hepatocyte Growth Factor