C-REACTIVE PROTEIN MODULATES HUMAN LUNG FIBROBLAST MIGRATION

Kazuhiko Kikuchi Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Tadashi Kohyama Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Yasuhiro Yamauchi Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Jun Kato Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Kazutaka Takami Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Hitoshi Okazaki Research and Development Department, Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan

Masashi Desaki Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Takahide Nagase Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Stephen I. Rennard Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, Nebraska, USA

Hajime Takizawa Fourth Department of Internal Medicine, Teikyo University, Tokyo, Japan

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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 μ g/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 μ M) and SB203580 (25 μ M) 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.

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C-REACTIVE PROTEIN MODULATES HUMAN LUNG FIBROBLAST MIGRATION

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C-REACTIVE PROTEIN MODULATES HUMAN LUNG FIBROBLAST MIGRATION

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