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

Chun Yu Lo, Charalambos Michaeloudes, Pankaj K. Bhavsar, Chien Da Huang, Po Jui Chang, Chun Hua Wang, Han Pin Kuo, Kian Fan Chung

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number194
JournalRespiratory Research
Volume18
Issue number1
DOIs
Publication statusPublished - Nov 21 2017
Externally publishedYes

Keywords

  • CAMP
  • Corticosteroids
  • Fibrocytes
  • Severe asthma
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Lo, C. Y., Michaeloudes, C., Bhavsar, P. K., Huang, C. D., Chang, P. J., Wang, C. H., Kuo, H. P., & Chung, K. F. (2017). Reduced suppressive effect of β2-adrenoceptor agonist on fibrocyte function in severe asthma. Respiratory Research, 18(1), [194]. https://doi.org/10.1186/s12931-017-0678-7