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Lentivirus-Mediated ADAM17 RNA Interference Inhibited Interleukin-8 Expression via EGFR Signaling in Lung Epithelial Cells

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Abstract

Interleukin (IL)-8 and neutrophil inflammation play a vital role in the pathogenesis of chronic inflammatory airway diseases. A disintegrin and metalloproteinase 17 (ADAM17) cleaves ectodomains of various transmembrane proteins and is an important regulator of almost every cellular event. The aim of this work was to investigate the roles of epidermal growth factor receptor (EGFR) signaling and ADAM17 in IL-8 expression induced by lipopolysaccharide (LPS) in A549 lung epithelial cells. In the present study, we found that transforming growth factor-α (TGF-α)-neutralizing Ab, EGFR-neutralizing Ab, and AG1478 significantly inhibited the phosphorylation of EGFR and IL-8 production induced by LPS. Lentivirus-mediated ADAM-17 RNA interference markedly inhibited ADAM-17 expression, the release of TGF-α, and the phosphorylation of EGFR and IL-8 expression. The results demonstrated that lentivirus-mediated RNA interference targeting ADAM17 suppressed IL-8 expression induced by LPS via inhibiting EGFR signaling, and ADAM17–EGFR signaling cascade mediated IL-8 production induced by LPS in lung epithelial cells.

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References

  1. Kobayashi, Y. 2008. The role of chemokines in neutrophil biology. Frontiers in Bioscience 13: 2400–2407.

    Article  PubMed  CAS  Google Scholar 

  2. Yokochi, S., and K. Matsushima. 2005. Chemokines. Nippon Rinsho 63: 220–225.

    PubMed  Google Scholar 

  3. Chen, W., M. Kajiya, G. Giro, K. Ouhara, H.E. Mackler, H. Mawardi, H. Boisvert, M.J. Duncan, K. Sato, and T. Kawai. 2010. Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells. Biochemical and Biophysical Research Communications 391: 645–650.

    Article  PubMed  CAS  Google Scholar 

  4. Yoon, B.N., N.G. Choi, H.S. Lee, K.S. Cho, and H.J. Roh. 2010. Induction of interleukin-8 from nasal epithelial cells during bacterial infection: the role of IL-8 for neutrophil recruitment in chronic rhinosinusitis. Mediators of Inflammation 2010: 813610.

    Article  PubMed  Google Scholar 

  5. Mulligan, R.M., C. Atkinson, A.A. Vertegel, V. Reukov, and R.J. Schlosser. 2009. Cigarette smoke extract stimulates interleukin-8 production in human airway epithelium and is attenuated by superoxide dismutase in vitro. American Journal of Rhinology & Allergy 23: e1–4.

    Article  Google Scholar 

  6. Quint, J.K., and J.A. Wedzicha. 2007. The neutrophil in chronic obstructive pulmonary disease. The Journal of Allergy and Clinical Immunology 119: 1065–1071.

    Article  PubMed  CAS  Google Scholar 

  7. Hamilton, L.M., C. Torres-Lozano, S.M. Puddicombe, A. Richter, I. Kimber, R.J. Dearman, B. Vrugt, R. Aalbers, S.T. Holgate, R. Djukanovi, S.J. Wilson, and D.E. Davies. 2003. The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma. Clinical and Experimental Allergy 33: 233–240.

    Article  PubMed  CAS  Google Scholar 

  8. Tabary, O., H. Corvol, E. Boncoeur, K. Chadelat, C. Fitting, J.M. Cavaillon, A. Clément, and J. Jacquot. 2006. Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions. American Journal of Physiology. Lung Cellular and Molecular Physiology 290: L588–596.

    Article  PubMed  CAS  Google Scholar 

  9. Pinto-Plata, V.M., G. Livnat, M. Girish, H. Cabral, P. Masdin, P. Linacre, R. Dew, L. Kenney, and B.R. Celli. 2007. Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD. Chest 131: 37–43.

    Article  PubMed  CAS  Google Scholar 

  10. Singh, D., L. Edwards, R. Tal-Singer, and S. Rennard. 2010. Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study. Respiratory Research 11: 77.

    Article  PubMed  Google Scholar 

  11. Lo, H.W. 2010. Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications. Discovery Medicine 10: 44–51.

    PubMed  Google Scholar 

  12. Burgel, P.R., and J.A. Nadel. 2008. Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. European Respiratory Journal 32: 1068–1081.

    Article  PubMed  CAS  Google Scholar 

  13. Sanderson, M.P., P.J. Dempsey, and A.J. Dunbar. 2006. Control of ErbB signaling through metalloprotease mediated ectodomain shedding of EGF-like factors. Growth Factors 24: 121–136.

    Article  PubMed  CAS  Google Scholar 

  14. Monika, G. 2010. ADAM-17: The enzyme that does it all. Critical Reviews in Biochemistry and Molecular Biology 45: 146–169.

    Article  Google Scholar 

  15. de Boer, W.I., C.M. Hau, A. van Schadewijk, J. Stolk, J.H. van Krieken, and P.S. Hiemstra. 2006. Expression of epidermal growth factors and their receptors in the bronchial epithelium of subjects with chronic obstructive pulmonary disease. American Journal of Clinical Pathology 125: 184–192.

    PubMed  Google Scholar 

  16. Rada, B., P. Gardina, T.G. Myers, and T.L. Leto. 2011. Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin. Mucosal Immunology 4: 158–171.

    Article  PubMed  CAS  Google Scholar 

  17. Allahverdian, S., N. Harada, G.K. Singhera, D.A. Knight, and D.R. Dorscheid. 2008. Secretion of IL-13 by Airway Epithelial Cells Enhances Epithelial Repair via HB-EGF. American Journal of Respiratory Cell and Molecular Biology 38: 153–160.

    Article  PubMed  CAS  Google Scholar 

  18. Hinkle, C.L., M.J. Mohan, P. Lin, N. Yeung, F. Rasmussen, M.E. Milla, and M.L. Moss. 2003. Multiple metalloproteinases process protransforming growth factor-alpha (proTGF-alpha). Biochemistry 42: 2127–2136.

    Article  PubMed  CAS  Google Scholar 

  19. Shao, M.X., and J.A. Nadel. 2005. Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 102: 767–772.

    Article  PubMed  CAS  Google Scholar 

  20. McGovern, T., P.A. Risse, K. Tsuchiya, M. Hassan, G. Frigola, and J.G. Martin. 2010. LTD4 induces HB-EGF-dependent CXCL8 release through EGFR activation in human bronchial epithelial cells. American Journal of Physiology. Lung Cellular and Molecular Physiology 299: L808–L815.

    Article  PubMed  CAS  Google Scholar 

  21. Burgess, A.W. 2008. EGFR family: structure physiology signalling and therapeutic targets. Growth Factors 26: 263–274.

    Article  PubMed  CAS  Google Scholar 

  22. Edwards, D.R., M.M. Handsley, and C.J. Pennington. 2008. The ADAM metalloproteinases. Molecular Aspects of Medicine 29: 258–289.

    Article  PubMed  CAS  Google Scholar 

  23. Charbonneau, M., K. Harper, F. Grondin, M. Pelmus, P.P. McDonald, and C.M. Dubois. 2007. Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by synovial cells. Journal of Biological Chemistry 282: 33714–33724.

    Article  PubMed  CAS  Google Scholar 

  24. Mochizuki, S., and Y. Okada. 2007. ADAMs in cancer cell proliferation and progression. Cancer Science 98: 621–628.

    Article  PubMed  CAS  Google Scholar 

  25. Angaji, S.A., S.S. Hedayati, R.H. Poor, S. Madani, S.S. Poor, and S. Panahi. 2010. Application of RNA interference in treating human diseases. Journal of Genetics 89: 527–537.

    Article  PubMed  Google Scholar 

  26. Schambach, A., and C. Baum. 2008. Clinical application of lentiviral vectors—concepts and practice. Current Gene Therapy 8: 474–482.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No_81000016) and the Medical Science Foundation of Zhejiang Province (No_2008B007).

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Authors and Affiliations

  1. Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, 158 Shangtang Road, Hangzhou, 310014, China

    Yaqing Li, Jianping Yan, Wulin Xu & Hong Wang

  2. Zhejiang Provincial Gastroenterology Key Laboratory, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, China

    Yingjie Xia

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  1. Yaqing Li
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  2. Jianping Yan
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  3. Wulin Xu
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  4. Hong Wang
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Correspondence to Yaqing Li.

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Li, Y., Yan, J., Xu, W. et al. Lentivirus-Mediated ADAM17 RNA Interference Inhibited Interleukin-8 Expression via EGFR Signaling in Lung Epithelial Cells. Inflammation 35, 850–858 (2012). https://doi.org/10.1007/s10753-011-9386-5

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  • DOI: https://doi.org/10.1007/s10753-011-9386-5

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