Cigarette smoke (CS)-induced airway inflammation is the main pathogenesis of COPD. The present study was designed to evaluate whether ghrelin, a novel growth hormone-releasing peptide, can affect the pro-inflammatory cytokine interleukin-6 (IL-6) production induced by cigarette smoke extract (CSE) in the human bronchial epithelial cell line (16-HBE) and its possible mechanism. 16-HBE cells were pre-incubated with vehicle or ghrelin (0.1 to 1000 ng/mL) in a concentration-dependent manner, and then CSE (0 to 16 %) was added. The protein levels of IL-6 in the medium were determined by ELISA, and the mRNA expressions of IL-6 was detected by RT-PCR. We also detected the phosphorylation of IKKα/β/p65 protein and the degradation of inhibitory protein-κB (I-κB) by Western blot analysis. And the generation of reactive oxygen species (ROS) in 16-HBE was evaluated by labeling specific fluorescence probes DCFH-DA. 16-HBE Cells treated with CSE (8 %) exhibited significantly higher IL-6 production compared with cells treated with vehicle alone (P < 0.05). Ghrelin suppressed CSE-induced IL-6 production at both mRNA and protein levels in a concentration-dependent manner (P < 0.05). Moreover, ghrelin attenuated CSE-triggered NF-κB activation in 16-HBE, but the intracellular ROS level after application of CSE was not affected by ghrelin (0.1 to 1000 ng/mL). Together, these results suggest that ghrelin inhibits CSE-induced IL-6 production in 16-HBE cells by targeting on NF-κB pathway, but not by scavenging intracellular ROS.
Keywords: NF-κB pathway; bronchial epithelia; cigarette smoke; ghrelin; interleukin-6.