Ghrelin Inhibits Interleukin-6 Production Induced by Cigarette Smoke Extract in the Bronchial Epithelial Cell Via NF-κB Pathway.
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.
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Hao
H
Wang
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Ting
T
Yang
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Yongchun
Y
Shen
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Chun
C
Wan
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Xiaoou
X
Li
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Diandian
D
Li
West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, China.
Yang
Y
Liu
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Tao
T
Wang
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Dan
D
Xu
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China.|Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Fuqiang
F
Wen
Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China. Docbwy@126.com.
Binwu
B
Ying
D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000276:immunology*; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D051996:Transcription Factor RelA / Q000378:metabolism*
D054439:Ghrelin; C508600:IL6 protein, human; D015850:Interleukin-6; C498143:RELA protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012906:Smoke; D051996:Transcription Factor RelA; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
NF-κB pathway; bronchial epithelia; cigarette smoke; ghrelin; interleukin-6