RAGE partially mediates cigarettes smoke extract induced cytokine and chemokine production in human bronchial epithelial cells

Alshehri, Mohammed; Brand, Oliver; Alqarni, Abdullah; Pasini, Alice; PANG, LINHUA

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.

Citation

Alshehri, M., Brand, O., Alqarni, A., Pasini, A., & PANG, L. (2018). RAGE partially mediates cigarettes smoke extract induced cytokine and chemokine production in human bronchial epithelial cells. European Respiratory Journal, 52(Suppl. 62), doi:10.1183/13993003.congress-2018.PA4246

• Journal Article Type: Conference Paper
• Conference Name: ERS International Congress
• Start Date: Sep 14, 2018
• End Date: Sep 19, 2018
• Acceptance Date: Sep 14, 2018
• Online Publication Date: Sep 14, 2018
• Publication Date: Sep 14, 2018
• Deposit Date: Dec 14, 2018
• Print ISSN: 0903-1936
• Publisher: European Respiratory Society
• Peer Reviewed: Peer Reviewed
• Volume: 52
• Issue: Suppl. 62
• Article Number: PA4246
• Pages: suppl 62:PA4246
• DOI: https://doi.org/10.1183/13993003.congress-2018.PA4246
• Public URL: https://nottingham-repository.worktribe.com/output/1416713
• Publisher URL: http://erj.ersjournals.com/content/52/suppl_62/PA4246