Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells.
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.
Yoshioka
T
T
First Department of Surgery, Okayama University Medical School, Japan.
Morimoto
Y
Y
Iwagaki
H
H
Itoh
H
H
Saito
S
S
Kobayashi
N
N
Yagi
T
T
Tanaka
N
N
D015703:Antigens, CD / Q000235:genetics; D003110:Colonic Neoplasms; D016207:Cytokines / Q000235:genetics; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006090:Gram-Negative Bacteria; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016207:Cytokines; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor