Effect of tiotropium bromide on airway remodeling in a chronic asthma model.
BACKGROUND
Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma.


OBJECTIVE
To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma.


METHODS
To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 μL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed.


RESULTS
In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide.


CONCLUSIONS
This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.
Division of Respiratory Medicine, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, South Korea. sooklee@catholic.ac.kr
Ji Young
JY
Kang
Chin Kook
CK
Rhee
Ju Sang
JS
Kim
Chan Kwon
CK
Park
Seung Joon
SJ
Kim
Sang Haak
SH
Lee
Hyung Kyu
HK
Yoon
Soon Seog
SS
Kwon
Young Kyoon
YK
Kim
Sook Young
SY
Lee
D000109:Acetylcholine / Q000378:metabolism; D000208:Acute Disease; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D002908:Chronic Disease; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D012602:Scopolamine Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D000069447:Tiotropium Bromide
D018680:Cholinergic Antagonists; D016207:Cytokines; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D012602:Scopolamine Derivatives; D010047:Ovalbumin; D000109:Acetylcholine; D000069447:Tiotropium Bromide