Carbon Monoxide Inhibits Cytokine and Chloride Secretion in Human Bronchial Epithelia

Abstract

Background/Aims: Carbon monoxide (CO) is an important gas produced endogenously by heme oxygenase (HO) that functions as an anti-inflammatory and in ion channel modulation, but the effects of CO on airway inflammation and ion transport remains unclear. Methods: The effect of CO on cell damage-and nucleotide-induced pro-inflammatory cytokine release in primary human bronchial epithelia cells (HBE) and in the 16HBE14o-human bronchial epithelial cell line were investigated. The effects of CO on calcium-and cAMP-dependent chloride (Cl - ) secretion were examined using a technique that allowed the simultaneous measurement and quantification of real-time changes in signalling molecules (cAMP and Ca 2+ ) and ion transport in a polarised epithelium. Results: CO suppressed the release of interleukin (IL)-6 and IL-8 and decreased the phosphorylation of ERK1/2 and NF-κB p65. Furthermore, CO inhibited UTP-induced increases in calcium and Cl - secretion, and forskolin-induced increases in cAMP and Cl - secretion. Conclusions: These findings suggest a novel anti-inflammatory role of CO in human bronchial epithelia via interactions with purinergic signalling pathways. Further, CO modulated both the Ca 2+ -and cAMP-dependent secretion of Cl - .