title: Activation of  COL1A2  promoter in human fibroblasts by  Escherichia coli.
abstract: 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.
authors.affiliation: Department of Microbiology, Tokyo Medical University, Tokyo, Japan. hmiya@tokyo-med.ac.jp
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Ryo
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Awano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D011112:Polymyxin B / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D024042:Collagen Type I; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D008156:Luciferases; D011112:Polymyxin B