title: C-reactive protein modulates human lung fibroblast migration.
abstract: C-reactive protein (CRP) has been classically used as a marker of inflammation. The aim of this study was to investigate the effect of CRP on migration of human fetal lung fibroblasts (HFL-1) to human plasma fibronectin (HFn). Using the blindwell chamber technique, CRP inhibited HFL-1 migration in a dose-dependent fashion (at 1 microg/mL, inhibition: 32.5% +/- 7.1%; P < .05). Western blot analysis showed that CRP inhibited the p38 mitogen-activated protein kinase (MAPK) activity in the presence of HFn. Moreover, the MAPK inhibitors SB202190 (25 microM) and SB203580 (25 microM) inhibited HFn-induced cell migration, suggesting an important role of p38 MAPK in HFn-induced migration. Taken together, these results suggest that the inhibitory effect of CRP is mediated by blocking MAPK. In summary, this study demonstrates that CRP directly modulates human lung fibroblasts migration. Thus, CRP may contribute to regulation of wound healing and may be endogenous antifibrotic factor acting on lung fibrosis.
authors.affiliation: Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Takami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Desaki
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
mesh_terms: D002097:C-Reactive Protein / Q000494:pharmacology*; D054443:Cell Migration Assays; D002464:Cell Migration Inhibition / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005353:Fibronectins; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D002097:C-Reactive Protein; D019810:Sodium Azide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole