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Reduced suppressive effect of β2-adrenoceptor agonist on fibrocyte function in severe asthma

Authors :
Chun-Yu Lo
Charalambos Michaeloudes
Pankaj K. Bhavsar
Chien-Da Huang
Po-Jui Chang
Chun-Hua Wang
Han-Pin Kuo
Kian Fan Chung
Source :
Respiratory Research, Vol 18, Iss 1, Pp 1-9 (2017)
Publication Year :
2017
Publisher :
BMC, 2017.

Abstract

Abstract Background Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. Methods Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram. Results Salmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface β2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased β2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation. Conclusions Fibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids.

Details

Language :
English
ISSN :
1465993X and 47774053
Volume :
18
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Respiratory Research
Publication Type :
Academic Journal
Accession number :
edsdoj.16c2d2ae47774053bb87aeb318276855
Document Type :
article
Full Text :
https://doi.org/10.1186/s12931-017-0678-7