RAGE Partially Mediates Cigarettes Smoke Extract induced Cytokine and Chemokine Production in Human Bronchial Epithelial Cells

Abstract

Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease. Cigarette smoke (CS) is known to be the major cause of COPD. RAGE is a 35 kDa protein member belonging to the immunoglobulin superfamily of cell surface receptors. RAGE plays a critical role in airway inflammation. However, the role of RAGE in mediating CSE-induced inflammatory cytokines/chemokines in human bronchial epithelial cells is poorly understood. Human bronchial epithelial cells (BEAS-2B) were treated with CSE. The effect of RAGE inhibitor (FPS-ZM1) on CSE-induced cytokine/chemokine production was explored to assess the role of RAGE. CXCL5, CCL11, CXCL1, CXCL10, IL-8, and IL-6 were analysed by ELISA. sRAGE secretion and RAGE expression were analysed by ELISA and Western blotting, respectively. Cell viability assay was conducted for CSE and FPS-ZM1. We found that CXCL1, CXCL5, CXCL10 and CCL11 could not be detected in untreated and CSE-treated cells, but the production of IL-8 and IL-6 was induced by CSE. sRAGE secretion was undetectable in untreated and CSE-treated cells. Interestingly, RAGE was highly expressed in untreated cells, and CSE did not further increase its expression. CSE-induced IL-8 and IL-6 production was partially inhibited by FPS-ZM1. FPS-ZM1 had no effect on RAGE expression. Our results suggest CS may contribute to the pathogenesis of COPD by modulating pulmonary function through IL-6 and modulating neutrophil-driven airway inflammation through IL-8. RAGE may play a role in mediating CSE-induced IL-8 and IL-6 production from human bronchial epithelial cells. Further studies are needed to knock down RAGE expression to confirm its role.