Resistin‐like molecule‐β is induced following bronchoconstriction of asthmatic airways

Grainge, Christopher L., Dulay, Valdeep, Ward, Jonathan, Sammut, David, Davies, Elizabeth, Green, Benjamin, Lau, Laurie C.K., Cottey, Laura, Haitchi, Hans-Michael, Davies, Donna E. and Howarth, Peter H. (2012) Resistin‐like molecule‐β is induced following bronchoconstriction of asthmatic airways. Respirology, 17 (7), 1094-1100. (doi:10.1111/j.1440-1843.2012.02215.x). (PMID:22758223)

Abstract

Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.

Methods: Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM‐β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM‐β mRNA.

Results: RELM‐β immunoreactivity, which co‐localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P < 0.001 between groups). RELM‐β immunoreactivity significantly and inversely correlated in asthma with forced expiratory volume in 1 s % predicted (P = 0.005). Acute changes in immunoexpression were evident after repeated inhalation challenge with allergen (2.15 % to 4.35 % (P = 0.01)) and methacholine (4.21 % to 6.16 % (P = 0.01)) but did not change in the salbutamol/methacholine challenge group. These changes correlated with change in basement membrane thickness (r = 0.38, P = 0.02). Epithelial RELM‐β gene expression was not altered in asthma.

Conclusions: RELM‐β may play an important role not only in animal models of airway remodelling, but also in human airway pathology.

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Contributors

Author: Jonathan Ward

Author: Elizabeth Davies

Author: Hans-Michael Haitchi

Author: Donna E. Davies

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