Abstract
Major basic protein (MBP) derived from activated eosinophil can exacerbate atopic asthma induced by lipopolysaccharide (LPS). The pharmacological function of MBP can be mimicked by poly-l-arginine (PLA), however, the potential signaling mechanisms of LPS-PLA-induced release of the inflammatory cytokines interleukin (IL)-6 and IL-8 remain unclear. In the present study, airway epithelia NCI-H292 cell lines were treated with LPS and/or PLA. We found that the expression levels of IL-6 and IL-8 induced by LPS-PLA were increased significantly compared with that in untreated cells. Meanwhile, the phosphorylation of p38 MAPK and ERK1/2 was also up-regulated dramatically by LPS-PLA, but this increase could be blocked by specific inhibitor. Importantly, blocking the phosphorylation of p38 MAPK and ERK1/2 reduced the expression levels of IL-6 and IL-8 as well. Collectively, LPS-PLA-induced release of IL-6 and IL-8 from NCI-H292 cells may be due to the synergistic activation of p38 MAPK and ERK1/2 signaling transduction pathways.
Similar content being viewed by others
References
Song, C., Y. Yuan, X.M. Wang, D. Li, G.M. Zhang, B. Huang, and Z.H. Feng. 2014. Passive transfer of tumour-derived MDSCs inhibits asthma-related airway inflammation. Scandinavian Journal of Immunology 79: 98–104.
Chen, B.C., C.C. Yu, H.C. Lei, M.S. Chang, M.J. Hsu, C.L. Huang, M.C. Chen, J.R. Sheu, T.F. Chen, T.L. Chen, H. Inoue, and C.H. Lin. 2004. Bradykinin B2 receptor mediates NF-Κb activation and cyclooxygenase-2 expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells. Journal of Immunology 173: 5219–5228.
Mattoli, S., S. Miante, F. Calabrò, M. Mezzetti, A. Fasoli, and L. Allegra. 1990. Bronchial epithelial cells exposed to isocyanates potentiate activation and proliferation of T-cells. American Journal of Physiology 259: L320–L327.
Soloperto, M., V.L. Mattoso, A. Fasoli, and S. Mattoli. 1991. A bronchial epithelial cell-derived factor in asthma that promotes eosinophil activation and survival as GM-CSF. American Journal of Physiology 260: L530–L538.
Mattoli, S., M. Marini, and A. Fasoli. 1991. Expression of the potent inflammatory cytokines, GM-CSF, IL6, and IL8, in bronchial epithelial cells of asthmatic patients. Chest 101: 27S–29S.
Marini, M., E. Vittori, J. Hollemborg, and S. Mattoli. 1992. Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. Journal of Allergy and Clinical Immunology 89: 1001–1009.
Hong, J.Y., K.E. Lee, K.W. Kim, M.H. Sohn, and K.E. Kim. 2010. Chitinase induce the release of IL-8 in human airway epithelial cells, via Ca2 + −dependent PKC and ERK pathways. Scandinavian Journal of Immunology 72: 15–21.
Hammad, H., M. Chieppa, F. Perros, M.A. Willart, R.N. Germain, and B.N. Lambrecht. 2009. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nature Medicine 15: 410–416.
Hernandez, M.L., B. Harris, J.C. Lay, P.A. Bromberg, D. Diaz-Sanchez, R.B. Devlin, S.R. Kleeberger, N.E. Alexis, and D.B. Peden. 2010. Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge. Inhalation Toxicology 22: 648–656.
Poynter, M.E. 2012. Airway epithelial regulation of allergic sensitization in asthma. Pulmonary Pharmacology & Therapeutics 25: 438–446.
Hernandez, M.L., M. Herbst, J.C. Lay, N.E. Alexis, W.J. Brickey, J.P. Ting, H. Zhou, and D.B. Peden. 2012. Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers. Journal of Allergy and Clinical Immunology 130: 869–876. e2.
Larsson, R., D. Rocksén, B. Lilliehöök, A. Jonsson, and A. Bucht. 2000. Dose-dependent activation of lymphocytes in endotoxin-induced airway inflammation. Infection and Immunity 68: 6962–6969.
Kirshenbaum, A.S., E. Swindle, M. Kulka, Y. Wu, and D.D. Metcalfe. 2008. Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition. BMC Immunology 9: 45.
Toward, T.J., and K.J. Broadley. 2000. Airway reactivity, inflammatory cell influx and nitric oxide in guinea-pig airways after lipopolysaccharide inhalation. British Journal of Pharmacology 131: 271–281.
Natarajan, S., J. Kim, J. Bouchard, W. Cruikshank, and D.G. Remick. 2011. Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: a randomized laboratory study. BMC Pulmonary Medicine 11: 12.
Folkerts, G., P.A. Henricks, P.J. Slootweg, and F.P. Nijkamp. 1988. Endotoxin-induced inflammation and injury of the guinea pig respiratory airways cause bronchial hyporeactivity. American Review of Respiratory Disease 137: 1441–1448.
Snella, M.C., and R. Rylander. 1982. Lung cell reactions after inhalation of bacterial lipopolysaccharides. European Journal of Respiratory Diseases 63: 550–557.
Xue, A., J. Wang, G.C. Sieck, and M.E. Wylam. 2010. Distribution of major basic protein on human airway following in vitro eosinophil incubation. Mediators of Inflammation 2010: 824362.
Shamri, R., J.J. Xenakis, and L.A. Spencer. 2011. Eosinophils in innate immunity: an evolving story. Cell and Tissue Research 343: 57–83.
Gleich, G.J. 2000. Mechanisms of eosinophil-associated inflammation. Journal of Allergy and Clinical Immunology 105: 651–663.
de Oliveira, P.C., P.O. de Lima, D.T. Oliveira, and M.C. Pereira. 2012. Eosinophil cationic protein: overview of biological and genetic features. DNA and Cell Biology 31: 1442–1446.
Hogan, S.P., H.F. Rosenberg, R. Moqbel, S. Phipps, P.S. Foster, P. Lacy, A.B.. Kay, and M.E. Rothenberg. 2008. Eosinophils: biological properties and role in health and disease. Clinical and Experimental Allergy 38: 709–750.
Shahana, S., C. Kampf, and G.M. Roomans. 2002. Effects of the cationic protein poly-L-arginine on airway epithelial cells in vitro. Mediators of Inflammation 11: 141–148.
Coyle, A.J., S.J. Ackerman, R. Burch, D. Proud, and C.G. Irvin. 1995. Human eosinopphil-granule major basic protein and synthetic polycations induce airway hyperresonpsiveness in vivo dependent on bradykinin generation. Journal of Clinical Investigation 95: 1735–1740.
Chow, A.W., J.F. Liang, J.S. Wong, Y. Fu, N.L. Tang, and W.H. Ko. 2010. Polarized secretion of interleukin (IL)-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge. PLoS One 5, e12091.
Fan, X.Y., A. van den Berg, M. Snoek, L.G. van der Flier, B. Smids, H.M. Jansen, R.Y. Liu, and R. Lutter. 2009. Arginine deficiency augments inflammatory mediator production by airway epithelial cells in vitro. Respiratory Research 10: 62.
Mercer, B.A., and J.M. D’Armiento. 2006. Emerging role of MAP kinase pathways as therapeutic targets in COPD. International Journal of Chronic Obstructive Pulmonary Disease 1: 137–150.
Liu, W., Q. Liang, S. Balzar, S. Wenzel, M. Gorska, and R. Alam. 2008. Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways. Journal of Allergy and Clinical Immunology 121: 893–902. e2.
Robins, S., L. Roussel, A. Schachter, P.A. Risse, A.K. Mogas, R. Olivenstein, J.G. Martin, Q. Hamid, and S. Rousseau. 2011. Steroid-insensitive ERK1/2 activity drives CXCL8 synthesis and neutrophilia by airway smooth muscle. American Journal of Respiratory Cell and Molecular Biology 45: 984–990.
Boots, A.W., K. Gerloff, R. Bartholomé, D. van Berlo, K. Ledermann, G.R. Haenen, A. Bast, F.J. van Schooten, C. Albrecht, and R.P. Schins. 2012. Neutrophils augment LPS-mediated pro-inflammatory signaling in human lung epithelial cells. Biochimica et Biophysica Acta 1823: 1151–1162.
Wang, Y.L., A.B.. Malik, Y. Sun, S. Hu, A.B.. Reynolds, R.D. Minshall, and G. Hu. 2011. Innate immune function of the adherens junction protein p120-catenin in endothelial response to endotoxin. Journal of Immunology 186: 3180–3187.
Muroya, M., K. Chang, K. Uchida, M. Bougaki, and Y. Yamada. 2012. Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549. Bioscience Trends 6: 70–80.
Zheng, X., D. Yang, X. Liu, N. Wang, B. Li, H. Cao, Y. Lu, G. Wei, H. Zhou, and J. Zheng. 2010. Identification of a new anti-LPS agent, geniposide, from Gardenia jasminoides Ellis, and its ability of direct binding and neutralization of lipopolysaccharide in vitro and in vivo. International Immunopharmacology 10: 1209–1219.
Schingnitz, U., K. Hartmann, C.F. Macmanus, T. Eckle, S. Zug, S.P. Colgan, and H.K. Eltzschig. 2010. Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury. Journal of Immunology 184: 5271–5279.
Rincon, M., and C.G. Irvin. 2012. Role of IL-6 in asthma and other inflammatory pulmonary diseases. International Journal of Biological Sciences 8: 1281–1290.
Pease, J.E., and I. Sabroe. 2002. The role of interleukin-8 and its receptors in inflammatory lung disease: implications for therapy. American Journal of Respiratory Medicine 1: 19–25.
Cabrera-Benitez, N.E., E. Pérez-Roth, M. Casula, A. Ramos-Nuez, C. Ríos-Luci, C. Rodríguez-Gallego, I. Sologuren, V. Jakubkiene, A.S. Slutsky, J.M. Padrón, and J. Villar. 2012. Anti-inflammatory activity of a novel family of aryl ureas compounds in an endotoxin-induced airway epithelial cell injury model. PLoS One 7, e48468.
Li, B., C. Dong, G. Wang, H. Zheng, X. Wang, and C. Bai. 2011. Pulmonary epithelial CCR3 promotes LPS-induced lung inflammation by mediating release of IL-8. Journal of Cellular Physiology 226: 2398–2405.
Chung, K.F. 2011. p38 mitogen-activated protein kinase pathways in asthma and COPD. Chest 139: 1470–1479.
Wang, C.B., C.K. Wong, W.K. Ip, M.L. Li, Y.P. Tian, and C.W. Lam. 2005. Induction of IL-6 in co-culture of bronchial epithelial cells and eosinophils is regulated by p38 MAPK and NF-kappaB. Allergy 60: 1378–1385.
Douillet, C.D., W.P. Robinson 3rd, P.M. Milano, R.C. Boucher, and P.B. Rich. 2006. Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways. American Journal of Physiology - Lung Cellular and Molecular Physiology 291: L734–L746.
Wong, C.K., C.B. Wang, W.K. Ip, Y.P. Tian, and C.W. Lam. 2005. Role of p38 MAPK and NF-kB for chemokine release in coculture of human eosinophils and bronchial epithelial cells. Clinical and Experimental Immunology 139: 90–100.
Li, W., Y.J. Xu, and H.H. Shen. 2007. Effect of cigarette smoke extract on lipopolysaccha-ride-activated mitogen-activated protein kinase signal transduction pathway in cultured cells. Chinese Medical Journal 120: 1075–1081.
Acknowledgments
This study was supported by the grants from the National Natural Science Foundation of China (81100027), Colleges and Universities Provincial Natural Science Research Project of Anhui (No KJ2011A176), Doctoral Initial Fund of the First Affiliated Hospital of Anhui Medical University, Academic and Scientific Research Activities of the Academic and Technical Leaders and Candidates of Anhui Provincial Human Resources and Social Security Department.
Conflict of Interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
Xiao-Yun Fan and Bing Chen contributed equally to this work.
Rights and permissions
About this article
Cite this article
Fan, XY., Chen, B., Lu, ZS. et al. Poly-l-Arginine Acts Synergistically with LPS to Promote the Release of IL-6 and IL-8 via p38/ERK Signaling Pathways in NCI-H292 Cells. Inflammation 39, 47–53 (2016). https://doi.org/10.1007/s10753-015-0221-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-015-0221-2