Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma

作者: S. Ohta , N. Oda , T. Yokoe , A. Tanaka , Y. Yamamoto

DOI: 10.1111/J.1365-2222.2010.03478.X

关键词:

摘要: Summary Background Tiotropium bromide, a long acting muscarinic receptor inhibitor, is potent agent for patients with bronchial asthma as well chronic obstructive pulmonary disease. Objective The aim of this study was to evaluate whether tiotropium bromide can inhibit allergen-induced acute and airway inflammation, T helper (Th)2 cytokine production, remodelling in murine model asthma. Methods Balb/c mice were sensitized challenged acutely or chronically ovalbumin (OVA). impact assessed using these models by histologic, morphometric, molecular techniques. Moreover, the effect on Th2 production from purified human peripheral blood mononuclear cells (PBMCs) assessed. Results Treatment significantly reduced inflammation bronchoalveolar lavage fluid (BALF) both asthma. levels TGF-β1 also BALF model. goblet cell metaplasia, thickness smooth muscle, fibrosis all decreased bromide-treated mice. hyperresponsiveness (AHR) serotonin abrogated spleen isolated OVA-sensitized inhibited 4-diphenylacetoxy-N-methylpiperidine methiodide, which selective antagonist M3 receptor. Finally, treatment PBMCs. Conclusion These results indicate that thus may reduce AHR asthma. Cite as: S. Ohta, N. Oda, T. Yokoe, A. Tanaka, Y. Yamamoto, Watanabe, K. Minoguchi, Ohnishi, Hirose, H. Nagase, Ohta M. Adachi, Clinical & Experimental Allergy, 2010 (40) 1266–1275.

参考文章(39)
Etsuko Tagaya, Jun Tamaoki, Mechanisms of Airway Remodeling in Asthma Allergology International. ,vol. 56, pp. 331- 340 ,(2007) , 10.2332/ALLERGOLINT.R-07-152
Sonja Matthiesen, Amit Bahulayan, Susanne Kempkens, Susanne Haag, Margarita Fuhrmann, Christine Stichnote, Uwe R. Juergens, Kurt Racké, Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. American Journal of Respiratory Cell and Molecular Biology. ,vol. 35, pp. 621- 627 ,(2006) , 10.1165/RCMB.2005-0343RC
Thais Mauad, Elisabeth H. Bel, Peter J. Sterk, Asthma therapy and airway remodeling The Journal of Allergy and Clinical Immunology. ,vol. 120, pp. 997- 1009 ,(2007) , 10.1016/J.JACI.2007.06.031
FRANCESCO SINIGAGLIA, DANIELE D'AMBROSIO, Regulation of Helper T Cell Differentiation and Recruitment in Airway Inflammation American Journal of Respiratory and Critical Care Medicine. ,vol. 162, ,(2000) , 10.1164/AJRCCM.162.SUPPLEMENT_3.15TAC3
SHU HASHIMOTO, YASUHIRO GON, IKUKO TAKESHITA, KEN MATSUMOTO, SHUICHIRO MARUOKA, TAKASHI HORIE, Transforming Growth Factor- β1 Induces Phenotypic Modulation of Human Lung Fibroblasts to Myofibroblast Through a c-Jun-NH2-Terminal Kinase-Dependent Pathway American Journal of Respiratory and Critical Care Medicine. ,vol. 163, pp. 152- 157 ,(2001) , 10.1164/AJRCCM.163.1.2005069
Yoshimichi Okayama, Chisei Ra, Hirohisa Saito, Role of mast cells in airway remodeling. Current Opinion in Immunology. ,vol. 19, pp. 687- 693 ,(2007) , 10.1016/J.COI.2007.07.018
Ignaz Wessler, Torsten Reinheimer, Heinz Kilbinger, Fernando Bittinger, Charles James Kirkpatrick, Joachim Saloga, Jürgen Knop, Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis. Life Sciences. ,vol. 72, pp. 2169- 2172 ,(2003) , 10.1016/S0024-3205(03)00079-1
M. Wegmann, H. Fehrenbach, A. Fehrenbach, T. Held, C. Schramm, H. Garn, H. Renz, Involvement of distal airways in a chronic model of experimental asthma. Clinical & Experimental Allergy. ,vol. 35, pp. 1263- 1271 ,(2005) , 10.1111/J.1365-2222.2005.02306.X
T Takahashi, M G Belvisi, H Patel, J K Ward, S Tadjkarimi, M H Yacoub, P J Barnes, Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. American Journal of Respiratory and Critical Care Medicine. ,vol. 150, pp. 1640- 1645 ,(1994) , 10.1164/AJRCCM.150.6.7952627
M. Longphre, D. Li, M. Gallup, E. Drori, C.L. Ordoñez, T. Redman, S. Wenzel, D. E. Bice, J.V. Fahy, C. Basbaum, Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells Journal of Clinical Investigation. ,vol. 104, pp. 1375- 1382 ,(1999) , 10.1172/JCI6097