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.