Abstract
As indicated in the Global Initiative for Asthma guidelines, short-acting β2-adrenoreceptor agonists (SABAs) are important relievers in asthma exacerbation. Interferon γ-inducible protein (IP)-10/CXCL 10 is a T-helper type 1 (Th1) cell-related chemokine which is important in the recruitment of Th1 cells involved in host immune defense against intracellular pathogens such as viral infection. Regulated on activation, normal T expressed and secreted (RANTES)/CCL 5 is a chemokine which plays a role in attractant of eosinophils, mast cells, and basophils toward the site of allergic inflammation. Bronchial epithelial cells are first-line barriers against pathogen invasion. However, whether SABAs have regulatory effects on the expression of IP-10 and RANTES in bronchial epithelial cells is unknown. BEAS-2B cells, the human bronchial epithelial cell lines, were pretreated with procaterol (one of the SABAs) or dibutyryl-cAMP (a cyclic AMP analog) at different doses for 1 h and then stimulated with poly I:C (10 μg/mL). Supernatants were collected 12 and 24 h after poly I:C stimulation to determine the concentrations of IP-10 and RANTES by ELISA. In some cases, the cells were pretreated with selective β2-adrenoreceptor antagonist, ICI-118551, 30 min before procaterol treatment. To investigate the intracellular signaling, the cells were pretreated with mitogen-activated protein kinase (MAPK) inhibitors and a NF-κB inhibitor 30 min before procaterol treatment. Western blot was also used to explore the intracellular signaling. Procaterol significantly suppressed poly I:C-induced IP-10 and RANTES in BEAS-2B cells in a dose-dependent manner. ICI-118551, a selective β2-adrenoreceptor antagonist, could significantly reverse the suppressive effects. Dibutyryl-cAMP could confer the similar effects of procaterol on poly I:C-induced IP-10 and RANTES expression. Data of Western blot revealed that poly I:C-induced p-ERK, p-JNK, and pp38 expression, but not pp65, were suppressed by procaterol. SABAs could suppress poly I:C-induced IP-10 and RANTES expression in bronchial epithelial cells, at least in part, via β2-adrenoreceptor-cAMP and MAPK-ERK, JNK, and p38 pathways.
Similar content being viewed by others
References
van Aalderen, W.M., A.B. Sprikkelman, and M.O. Hoekstra. 1999. Is childhood asthma an inflammatory disease? Allergy 54((Suppl 49)): 62–67.
Woodfolk, J.A. 2007. T-cell responses to allergens. The Journal of Allergy and Clinical Immunology 119: 280–294.
Barnes, P.J., K.F. Chung, and C.P. Page. 1998. Inflammatory mediators of asthma: An update. Pharmacological Reviews 50: 515–596.
Akdis, M., and C.A. Akdis. 2007. Mechanisms of allergen-specific immunotherapy. The Journal of Allergy and Clinical Immunology 119: 780–789.
Cockcroft, D.W., and B.E. Davis. 2006. Mechanisms of airway hyperresponsiveness. The Journal of Allergy and Clinical Immunology 118: 551–559.
Rosenberg, H.F., S. Phipps, and P.S. Foster. 2007. Eosinophil trafficking in allergy and asthma. The Journal of Allergy and Clinical Immunology 119: 1303–1310.
Tamura, S., and T. Kurata. 2004. Defense mechanisms against influenza virus infection in the respiratory tract mucosa. Japanese Journal of Infectious Diseases 57: 236–247.
Ono, S.J., T. Nakamura, D. Miyazaki, M. Ohbayashi, M. Dawson, and M. Toda. 2003. Chemokines: Roles in leukocyte development, trafficking, and effector function. The Journal of Allergy and Clinical Immunology 111: 1185–1199.
Zimmermann, N., G.K. Hershey, P.S. Foster, and M.E. Rothenberg. 2003. Chemokines in asthma: Cooperative between chemokines & IL-13. The Journal of Allergy and Clinical Immunology 111: 227–242.
Busse, W.W., and R.F. Lemanske. 2001. Asthma. The New England Journal of Medicine 344: 350–362.
Qin, S., J.B. Rottman, P. Myers, N. Kassam, M. Weinblatt, M. Loetscher, A.E. Koch, B. Moser, and C.R. Mackay. 1998. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. Journal of Clinical Investigation 101: 746–754.
Medoff, B.D., A. Sauty, A.M. Tager, J.A. Maclean, R.N. Smith, A. Mathew, J.H. Dufour, and A.D. Luster. 2002. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. Journal of Immunology 168: 5278–5286.
Wark, P.A., F. Bucchieri, S.L. Johnston, P.G. Gibson, L. Hamilton, J. Mimica, G. Zummo, S.T. Holgate, J. Attia, A. Thakkinstian, and D.E. Davies. 2007. IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations. The Journal of Allergy and Clinical Immunology 120: 586–593.
Lai, S.T., C.H. Hung, Y.M. Hua, S.H. Hsu, Y.J. Jong, and J.L. Suen. 2008. T-helper 1-related chemokines in the exacerbation of childhood asthma. Pediatrics International 50: 99–102.
Bateman, E.D., S.S. Hurd, P.J. Barnes, J. Bousquet, J.M. Drazen, M. FitzGerald, P. Gibson, K. Ohta, P. O’Byrne, S.E. Pedersen, E. Pizzichini, S.D. Sullivan, S.E. Wenzel, and H.J. Zar. 2008. Global strategy for asthma management and prevention: GINA executive summary. The European Respiratory Journal 31: 143–178.
Nelson, H.S. 2006. Is there a problem with inhaled long-acting beta-adrenergic agonists? The Journal of Allergy and Clinical Immunology 117: 3–16.
Smucny, J.J., C.A. Flynn, L.A. Becker, and R.H. Glazier. 2001. Are beta2-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systemic review. The Journal of Family Practice 50: 945–951.
Ritter, M., D. Mennerich, A. Weith, and P. Seither. 2005. Characterization of Toll-like receptors in primary lung epithelial cells: Strong impact of the TLR3 ligand poly(I:C) on the regulation of Toll-like receptors, adaptor proteins and inflammatory response. J Inflamm (Lond) 2: 16.
Stowell, N.C., J. Seideman, H.A. Raymond, K.A. Smalley, R.J. Lamb, D.D. Egenolf, P.J. Bugelski, L.A. Murray, P.A. Marsters, R.A. Bunting, R.A. Flavell, L. Alexopoulou, L.R. San Mateo, D.E. Griswold, R.T. Sarisky, M.L. Mbow, and A.M. Das. 2009. Long-term activation of TLR3 by poly(I:C) induces inflammation and impairs lung function in mice. Respiratory Research 10: 43.
Bérubé, J., C. Bourdon, Y. Yao, and S. Rousseau. 2009. Distinct intracellular signaling pathways control the synthesis of IL-8 and RANTES in TLR1/TLR2, TLR3 or NOD1 activated human airway epithelial cells. Cellular Signalling 21: 448–456.
Hallsworth, M.P., C.H. Twort, T.H. Lee, and S.J. Hirst. 2001. Beta 2-adrenoceptor agonists inhibit release of eosinophil activating cytokines from human airway smooth muscle cells. British Journal of Pharmacology 132: 729–741.
Koyama, S., E. Sato, T. Masubuchi, A. Takamizawa, K. Kubo, S. Nagai, and T. Isumi. 1999. Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity. The European Respiratory Journal 14: 767–775.
Tashimo, H., N. Yamashita, H. Ishida, H. Nagase, T. Adachi, J. Nakano, K. Yamamura, T. Yano, H. Yoshihara, and K. Ohta. 2007. Effect of procaterol, a beta(2) selective adrenergic receptor agonist, on airway inflammation and hyperresponsiveness. Allergology International 56: 241–247.
Horikoshi, S., F. Kokubu, and M. Adachi. 1996. Anti-allergic effects of beta-adrenoceptor agonists in the clinical pharmacological studies. Nippon Rinsho 54: 3068–3072.
Tomerak, A.A., H. Vyas, M. Lakenpaul, J.J. McGlashan, and M. McKean. 2005. Inhaled beta2-agonists for treating non-specific chronic cough in children. Cochrane Database Syst Rev. CD005373.
Bradding, P., I. Rushby, J. Scullion, and M.D. Morgan. 1999. As-required versus regular neubulized salbutamol for the treatment of acute severe asthma. The European Respiratory Journal 13: 290–294.
Kemper, M.J., E. Harps, H.H. Hellwege, and D.E. Müller-Wiefel. 1996. Effective treatment of acute hyperkalaemia in childhood by short-term infusion of salbutamol. European Journal of Pediatrics 155: 495–497.
Helfrich, E., T.W. de Vries, and E.N. van Roon. 2001. Salbutamol for hyperkalaemia in children. Acta Paediatrica 90: 1213–1216.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lam, KP., Chu, YT., Kuo, CH. et al. Suppressive Effects of Procaterol on Expression of IP-10/CXCL 10 and RANTES/CCL 5 by Bronchial Epithelial Cells. Inflammation 34, 238–246 (2011). https://doi.org/10.1007/s10753-010-9229-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-010-9229-9