Role of Wnt-1, Wnt-3 and MMP-7 in fibrotic response in extrinsic allergic alveolitis and idiopathic pulmonary fibrosis

Abstract

Aim: of proposed study is to investigate effect of Wnt-1, Wnt-3 and MMP-7 on fibrotic response in HP and IPF patients. IPF (n=11) or HP (n=7) patients were included into the prospective study. They underwent lung function tests and bronchoscopy with bronchoalveolar lavage at the time of diagnosis. Bronchoalveolar lavage fluid (BALF) was centrifuged. Extent and pattern of lung involvement were assessed by high resolution computed tomography (HRCT). Primary human lung fibroblasts were cultured in standard conditions. After confluency was reached media had been aspired and stored at -80°C (control group). Cells were exposed to BALF of patients and tumor growth factor (TGF) -beta. After 24 hours of exposure supernatants were aspired and stored at -80°C. Concentrations of Wnt-1, Wnt-3 and MMP-7 in control group supernatants, in supernatants harvested after exposure to patients BALF and after exposure to TGF-beta were measured. Significant difference between concentrations of MMP-7 after exposure to BALF of IPF and HP patients was found (p‹0,01). Concentrations of MMP-7 in supernatants after exposure to BALF positively correlated with age of patients (p<0,05) and negatively with HRCT alveolar score (p<0,05). Positive correlation between age of patients and HRCT interstitial score was observed (p<0,01). MMP-7 secretion by human lung fibroblasts changes singnificantly after exposure of cells to BALF of patients with IPF and HP. These differences seem to be age and extent of inflammation related. While age-related factors may play important role in fibrotic type of healing, inflammatory milieu might have protective anti-fibrotic role.