β2-Agonist clenbuterol hinders human monocyte differentiation into dendritic cells

Clenbuterol (CLB) is a beta2-adrenergic agonist commonly used in asthma therapy, but is also a non-steroidal anabolic drug often abused in sport doping practices. Here we evaluated the in vitro impact of CLB on the physiology and function of human monocytes and dendritic cells (DCs), instrumental in...

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Bibliographic Details
Published in:Experimental cell research 2015-12, Vol.339 (2), p.163-173
Main Authors: Giordani, Luciana, Cuzziol, Noemi, Del Pinto, Tamara, Sanchez, Massimo, Maccari, Sonia, Massimi, Alessia, Pietraforte, Donatella, Viora, Marina
Format: Article
Language:English
Subjects:
Adrenergic beta-2 Receptor Agonists - pharmacology
Cell Differentiation - drug effects
Cell Differentiation - immunology
Cells, Cultured
Clenbuterol
Clenbuterol - pharmacology
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Doping drugs
Dose-Response Relationship, Drug
Humans
Monocytes - cytology
Monocytes - drug effects
Monocytes - immunology
Monocytes Dendritic cells
Structure-Activity Relationship
β2-adrenoceptor agonist
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Summary:Clenbuterol (CLB) is a beta2-adrenergic agonist commonly used in asthma therapy, but is also a non-steroidal anabolic drug often abused in sport doping practices. Here we evaluated the in vitro impact of CLB on the physiology and function of human monocytes and dendritic cells (DCs), instrumental in the development of immune responses. We demonstrate that CLB inhibits the differentiation of monocytes into DCs and this effect is specific and dependent on β2-adrenergic receptor (AR) activation. We found that CLB treatment reduced the percentage of CD1a+ immature DCs, while increasing the frequency of monocytes retaining CD14 surface expression. Moreover, CLB inhibited tumor necrosis factor-alpha (TNF-alpha) enhanced IL-(interleukin)-10 and IL-6 production. In contrast, CLB did not modulate the phenotypic and functional properties of monocytes and DCs, such as the surface expression of HLA-DR, CD83, CD80 and CD86 molecules, cytokine production, immunostimulatory activity and phagocytic activity. Moreover, we found that CLB did not modulate the activation of NF-kB in DCs. Moreover, we found that the differentiation of monocytes into DCs was associated with a significant decrease of β2-ARs mRNA expression. These results provide new insights on the effect of CLB on monocyte differentiation into DCs. Considering the frequent illegal use of CLB in doping, our work suggests that this drug is potentially harmful to immune responses decreasing the supply of DCs, thus subverting immune surveillance. •Clenbuterol is a β2-adrenoreceptor agonist.•We study the impact of clenbuterol on human monocyte and monocyte-derived DC biology.•Clenbuterol inhibits the differentiation of monocytes into DCs.•Clenbuterol inhibits TNF-α and enhances IL-10 production.•The differentiation of monocytes into DCs is associated with decrease of β2-ARs mRNA.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2015.10.032