Tuberc Respir Dis.  2019 Jan;82(1):71-80. 10.4046/trd.2018.0049.

Expression of Muscarinic Receptors and the Effect of Tiotropium Bromide in Aged Mouse Model of Chronic Asthma

Affiliations
  • 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. youngkim@catholic.ac.kr

Abstract

BACKGROUND
Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling.
METHODS
BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined.
RESULTS
Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA.
CONCLUSION
Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Keyword

Receptors, Muscarinic; Ageing; Asthma; Tiotropium Bromide; Airway Remodeling

MeSH Terms

Actins
Aged
Airway Remodeling
Animals
Asthma*
Eosinophils
Female
Humans
Hydroxyproline
Interleukin-13
Interleukin-5
Interleukins
Mice*
Ovalbumin
Ovum
Pneumonia
Receptors, Muscarinic*
Tiotropium Bromide*
Actins
Hydroxyproline
Interleukin-13
Interleukin-5
Interleukins
Ovalbumin
Receptors, Muscarinic
Tiotropium Bromide
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