S100A12 Induce Pro‐inflammatory Response in Pulmonary Fibroblasts

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by a chronic and irreversible airflow obstruction that is associated to structural changes of the airway wall (remodeling). The major sites of remodeling in COPD are the bronchioles. The tissue remodeling process starts with epithelial damage followed by an inflammatory response that propagates into the underlying tissues. S100A12 is a member of the S100 protein family that is elevated in numerous chronic inflammatory diseases and that triggers cellular activation in endothelial cells, and leukocytes through its binding to RAGE receptor. Systemic S100A12 is elevated in IPF and cystic fibrosis. In the present report to assess the role of S100A12/RAGE in the pathogenesis of COPD, S100A12 concentration was measure in bronchoalveolar lavages (BAL), from healthy and COPD patients by ELISA. The expression of S100A12 and RAGE were studied in primary cultures of pulmonary fibroblasts (Fb) and human bronchial epithelial (HBE) cells by qPCR and IF. Pro‐inflammatory IL‐6 and GRO‐α expression were assessed by qPCR in Fb and HBE cultures exposed to S100A12. We found that S100A12 was significantly increased in BAL samples of COPD when compared to healthy individuals. We also found that while both Fb and HBE cells express RAGE, only HBE produce S100A12. When cell cultures were exposed we found that 100A12 significant increase IL‐6 and GRO‐α mRNA expression in Fb. No significant differences were found in HBE cells compared to untreated controls. These results suggest a possible role of S100A12 released by bronchial epithelium in inducing inflammatory response in Fb.