C-reactive protein modulates human lung fibroblast migration.
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.
Kikuchi
Kazuhiko
K
Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan.
Kohyama
Tadashi
T
Yamauchi
Yasuhiro
Y
Kato
Jun
J
Takami
Kazutaka
K
Okazaki
Hitoshi
H
Desaki
Masashi
M
Nagase
Takahide
T
Rennard
Stephen I
SI
Takizawa
Hajime
H
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
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