Journal Mobile Options
Table of Contents
Vol. 155, Suppl. 1, 2011
Issue release date: June 2011

Inhibition of Eosinophil Activation Mediated by a Toll-Like Receptor 7 Ligand with a Combination of Procaterol and Budesonide

Hiraguchi Y. · Tanida H. · Hosoki K. · Nagao M. · Tokuda R. · Fujisawa T.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: Viral respiratory tract infections play an important role in the inception and exacerbation of asthma. Eosinophils, major effector cells in asthma, often accumulate in the airways during viral infections and are possibly activated by respiratory RNA viruses through Toll-like receptor (TLR) 7. We investigated the effect of a β2-agonist, i.e. procaterol, and a corticosteroid, i.e. budesonide, that are commonly used for viral-induced asthma, on TLR7 ligand-induced activation of eosinophils in vitro. Methods: Purified peripheral blood eosinophils were incubated with procaterol and/or budesonide and stimulated with a TLR7 ligand, i.e. R-837. Expression of CD11b was analyzed by flow cytometry. Superoxide generation was measured via the cytochrome C reduction method. IL-8 in the supernatants was assayed by ELISA. Results: Although procaterol or budesonide alone did not inhibit R-837-induced CD11b expression, combinations of the 2 drugs significantly inhibited CD11b. Likewise, the combinations significantly inhibited O2 generation at low concentrations. Budesonide significantly inhibited R-837-induced IL-8 production in a concentration-dependent manner, and procaterol potentiated inhibition by budesonide although single-agent procaterol had no effect. Conclusion: A combination of procaterol and budesonide inhibits the TLR7-mediated effector function of eosinophils, indicating their possible anti-inflammatory effect for virus-induced asthma.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Jackson DJ, Johnston SL: The role of viruses in acute exacerbations of asthma. J Allergy Clin Immunol 2010;125:1178–1187, quiz 1188–1179.
  2. Guilbert TW, Denlinger LC: Role of infection in the development and exacerbation of asthma. Expert Rev Respir Med 2010;4:71–83.
  3. Harrison AM, Bonville CA, Rosenberg HF, Domachowske JB: Respiratory syncytial virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation. Am J Respir Crit Care Med 1999;159:1918–1924.
  4. Everard ML, Swarbrick A, Wrightham M, McIntyre J, Dunkley C, James PD, Sewell HF, Milner AD: Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Arch Dis Child 1994;71:428–432.
  5. Garofalo R, Kimpen JL, Welliver RC, Ogra PL: Eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection. J Pediatr 1992;120:28–32.
  6. Matthews SP, Tregoning JS, Coyle AJ, Hussell T, Openshaw PJ: Role of ccl11 in eosinophilic lung disease during respiratory syncytial virus infection. J Virol 2005;79:2050–2057.
  7. Johnson TR, Parker RA, Johnson JE, Graham BS: Il-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge. J Immunol 2003;170:2037–2045.
  8. Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, Foster PS, Matthaei KI: Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007;110:1578–1586.
  9. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA: Recognition of single-stranded RNA viruses by toll-like receptor 7. Proc Natl Acad Sci USA 2004;101:5598–5603.
  10. Nagase H, Okugawa S, Ota Y, Yamaguchi M, Tomizawa H, Matsushima K, Ohta K, Yamamoto K, Hirai K: Expression and function of toll-like receptors in eosinophils: activation by toll-like receptor 7 ligand. J Immunol 2003;171:3977–3982.
  11. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O’Byrne P, Barnes PJ, Ullman A: Effect of inhaled formoterol and budesonide on exacerbations of asthma – Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med 1997;337:1405–1411.
  12. Kavuru M, Melamed J, Gross G, Laforce C, House K, Prillaman B, Baitinger L, Woodring A, Shah T: Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2000;105:1108–1116.
  13. Fujisawa T, Kato Y, Terada A, Iguchi K, Kamiya H: Synergistic effect of theophylline and procaterol on interleukin-5-induced degranulation from human eosinophils. J Asthma 2002;39:21–27.
  14. Yoshimura T, Kurita C, Nagao T, Usami E, Nakao T, Watanabe S, Kobayashi J, Yamazaki F, Tanaka H, Inagaki N, Nagai H: Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Pharmacology 1997;54:144–152.
  15. Mirza ZN, Tokuyama K, Arakawa H, Kato M, Mochizuki H, Morikawa A: Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation. Clin Exp Allergy 1998;28:644–652.
  16. Tashimo H, Yamashita N, Ishida H, Nagase H, Adachi T, Nakano J, Yamamura K, Yano T, Yoshihara H, Ohta K: Effect of procaterol, a beta(2) selective adrenergic receptor agonist, on airway inflammation and hyperresponsiveness. Allergol Int 2007;56:241–247.
  17. Yoshida N, Muraguchi M, Kamata M, Ikezono K, Mori T: Procaterol potentiates the anti-inflammatory activity of budesonide on eosinophil adhesion to lung fibroblasts. Int Arch Allergy Immunol 2009;150:352–358.
  18. Fujisawa T, Kato Y, Nagase H, Atsuta J, Terada A, Iguchi K, Kamiya H, Morita Y, Kitaura M, Kawasaki H, Yoshie O, Hirai K: Chemokines induce eosinophil degranulation through CCR-3. J Allergy Clin Immunol 2000;106:507–513.
  19. Hiraguchi Y, Nagao M, Hosoki K, Tokuda R, Fujisawa T: Neutrophil proteases activate eosinophil function in vitro. Int Arch Allergy Immunol 2008;146(suppl 1):16–21.
  20. Mansson A, Cardell LO: Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils. J Leukoc Biol 2009;85:719–727.
  21. Wong CK, Cheung PF, Ip WK, Lam CW: Intracellular signaling mechanisms regulating Toll-like receptor-mediated activation of eosinophils. Am J Respir Cell Mol Biol 2007;37:85–96.
  22. Okubo Y, Hossain M, Horie S, Momose T, Suzuki J, Isobe M, Sekiguchi M: Inhibitory effects of theophylline and procaterol on eosinophil function. Intern Med 1997;36:276–282.
  23. Tachibana A, Kato M, Kimura H, Fujiu T, Suzuki M, Morikawa A: Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions. Clin Exp Immunol 2002;130:415–423.
  24. Yasui K, Kobayashi N, Yamazaki T, Agematsu K, Matsuzaki S, Nakata S, Baba A: Differential effects of short-acting beta2-agonists on human granulocyte functions. Int Arch Allergy Immunol 2006;139:1–8.
  25. Ueki S, Usami A, Oyamada H, Saito N, Chiba T, Mahemuti G, Ito W, Kato H, Kayaba H, Chihara J: Procaterol upregulates peroxisome proliferator-activated receptor-gamma expression in human eosinophils. Int Arch Allergy Immunol 2006;140(suppl 1):35–41.
  26. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, Gibson P, Ohta K, O’Byrne P, Pedersen SE, Pizzichini E, Sullivan SD, Wenzel SE, Zar HJ: Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143–178.
  27. Aksoy MO, Mardini IA, Yang Y, Bin W, Zhou S, Kelsen SG: Glucocorticoid effects on the beta-adrenergic receptor-adenylyl cyclase system of human airway epithelium. J Allergy Clin Immunol 2002;109:491–497.
  28. Usmani OS, Ito K, Maneechotesuwan K, Ito M, Johnson M, Barnes PJ, Adcock IM: Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med 2005;172:704–712.
  29. Kaur M, Chivers JE, Giembycz MA, Newton R: Long-acting beta2-adrenoceptor agonists synergistically enhance glucocorticoid-dependent transcription in human airway epithelial and smooth muscle cells. Mol Pharmacol 2008;73:203–214.
  30. Edwards MR, Johnson MW, Johnston SL: Combination therapy: synergistic suppression of virus-induced chemokines in airway epithelial cells. Am J Respir Cell Mol Biol 2006;34:616–624.
  31. Liu YJ: Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med 2006;203:269–273.
  32. Harada M, Hirota T, Jodo AI, Hitomi Y, Sakashita M, Tsunoda T, Miyagawa T, Doi S, Kameda M, Fujita K, Miyatake A, Enomoto T, Noguchi E, Masuko H, Sakamoto T, Hizawa N, Suzuki Y, Yoshihara S, Adachi M, Ebisawa M, Saito H, Matsumoto K, Nakajima T, Mathias RA, Rafaels N, Barnes KC, Himes BE, Duan QL, Tantisira KG, Weiss ST, Nakamura Y, Ziegler SF, Tamari M: TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma. Am J Respir Cell Mol Biol 2010, E-pub ahead of print.
  33. Prazma CM, Kral KM, Gul N, Yancey SW, Stempel DA: Controller medications and their effects on asthma exacerbations temporally associated with upper respiratory infections. Respir Med 2010;104:780–787.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50