C-reactive protein induces the expression of tissue factor and interleukin-8 in the lung

Abstract number: OC090

Gabazza E. C., Nakano M., Ohta K., Hayashi T., Kamada H., Taguchi O., Adachi Y., Suzuki K.

Mie University School of Medicine, Japan

C-reactive protein (CRP) is a unique serum pentraxin and the prototype acute phase protein. Previous studies have shown that CRP can induce production of inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and tissue factor (TF), the main initiator of coagulation cascade, in monocytes. We have previously shown that activation of the coagulation system plays a critical role in the pathogenesis of lung fibrosis. The present study was undertaken to evaluate the relationship of CRP with interleukin-8 (IL-8) and coagulation activation in lung fibrosis patients, and to assess the effect of CRP on IL-8 and TF in alveolar epithelial cells. This study comprised 62 patients with interstitial lung disease and 6 healthy subjects. A549 alveolar epithelial cell lines were used for the in vitro studies. The concentrations in bronchoalveolar lavage fluid (BALF) of CRP, IL-8 and thrombin–antithrombin complex (TAT), a marker of coagulation activation were measured by enzyme-linked immunoassay. The concentrations of CRP, IL-8, and TAT were significantly increased in BALF of interstitial lung disease patients compared to control subjects. CRP was significantly and proportionally associated with IL-8 and TAT. CRP stimulation induced the expression of IL-8 and TF from A549 cells in a dose-dependent fashion. These results suggest that CRP may increase the inflammatory response and the activation of the coagulation system in the lung by promoting the expression of IL-8 and TF from alveolar epithelial cells.