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Ghrelin Inhibits Interleukin-6 Production Induced by Cigarette Smoke Extract in the Bronchial Epithelial Cell Via NF-κB Pathway

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Abstract

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.

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Acknowledgments

This study was supported by grants 30900658 from the National Natural Science Foundation of China (NSFC) to Dr. Binwu Ying, 81300011 from the NSFC to Dr. Ting Yang, 31171103 and 81230001 from the NSFC and 06–834 from the China Medical Board of New York to Dr Fuqiang Wen.

Conflicts of Interest

The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China

      Hao Wang, Ting Yang, Yongchun Shen, Chun Wan, Xiaoou Li, Diandian Li, Tao Wang, Dan Xu & Fuqiang Wen

    2. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China

      Hao Wang, Ting Yang, Yongchun Shen, Chun Wan, Xiaoou Li, Diandian Li, Tao Wang, Dan Xu & Fuqiang Wen

    3. West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, China

      Yang Liu

    4. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China

      Binwu Ying

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    1. Hao Wang
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    Correspondence to Binwu Ying.

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    Hao Wang, Ting Yang and Yongchun Shen contributed equally to this work.

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    Wang, H., Yang, T., Shen, Y. et al. Ghrelin Inhibits Interleukin-6 Production Induced by Cigarette Smoke Extract in the Bronchial Epithelial Cell Via NF-κB Pathway. Inflammation 39, 190–198 (2016). https://doi.org/10.1007/s10753-015-0238-6

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    • DOI: https://doi.org/10.1007/s10753-015-0238-6

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