Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells.
Salmeterol is a long-acting β2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells (DCs) are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol (10(-5) mol/l) reduced the inflammation caused by lipopolysaccharide (0.1 µg/ml) in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.
Department of Respiratory Medicine, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
Zhenli
Z
Hu
Ruohua
R
Chen
Zhijian
Z
Cai
Lei
L
Yu
Yang
Y
Fei
Lixia
L
Weng
Jinghan
J
Wang
Xiahui
X
Ge
Tianyi
T
Zhu
Jianli
J
Wang
Chong
C
Bai
D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage; D000068299:Salmeterol Xinafoate
D058666:Adrenergic beta-2 Receptor Agonists; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000068299:Salmeterol Xinafoate; D010047:Ovalbumin; D000420:Albuterol