Alpha-defensin enhances expression of HSP47 and collagen-1 in human lung fibroblasts.

Abstract Neutrophils and lung fibroblasts are thought to play a role in the pathogenesis of pulmonary fibrosis. We reported previously that heat shock protein 47 (HSP47), a collagen-specific molecular chaperon, and collagen-1 synthesis were involved in pulmonary fibrosis, and that plasma levels of α-defensins (HNP; human neutrophil peptide), cationic proteins with antimicrobial and cytotoxic activity in neutrophils, were significantly higher in patients with idiopathic pulmonary fibrosis than in control subjects. Here, we investigated the direct effect of HNP-1 in vitro on the expression of HSP47 and collagen-1 in human lung fibroblasts (NHLF). HNP-1 at 5 μg/ml induced fibroblast proliferation but at concentrations > 50 μg/ml, HNP-1 reduced cell viability. Incubation of NHLF with 10 to 25 μg/ml of HNP-1 for 24-h increased the expression of HSP47 and collagen-1 mRNAs ( p p