Activation of COL1A2 promoter in human fibroblasts by Escherichia coli

The relationship between bacterial infection and collagen production was investigated using human fibroblasts transfected with the promoter of COL1A2 , which encodes the α1 chain of human type I collagen, linked to a luciferase reporter. The cells were used to assess the gene promoter activity of COL1A2 following bacterial stimulation. The COL1A2 promoter was activated by stimulation with fixed Escherichia coli in a dose-dependent manner, but not by fixed Staphylococcus aureus. Enhancement of collagen production was observed in the E.?coli-stimulated fibroblasts compared to those without stimulation. Both anti-human Toll-like receptor (TLR) 4 antibody and polymyxin B clearly blocked the COL1A2 promoter activity stimulated by E.?coli, while antibodies against human TLR2 and human transforming growth factor-β (TGF-β) receptor type II did not. These results indicate that E.?coli can directly interact with TLR4 expressed on the surface of fibroblasts and can further induce human type I collagen gene expression and collagen production in these cells. These data also suggest that infection by gram-negative bacteria may cause fibrosis.