Exposure to cigarette smoke downregulates β₂-adrenergic receptor expression and upregulates inflammation in alveolar macrophages

Abstract

Cigarette smoke-triggered inflammation is important in the pathophysiology of chronic obstructive pulmonary disease (COPD). β₂-Adrenergic receptor (β₂-AR) is abundantly expressed on inflammatory cells, which is associated with inflammation regulation. To observe alterations in inflammation, pathological changes in lung tissues, and detect changes in β₂-AR expression, rats were exposed for 4 months to cigarette smoke. Pathological changes were observed in lung tissue sections. The levels of inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF), and lung tissues were measured using enzyme-linked immunosorbent assay (ELISA). Nuclear factor (NF)-κB activity was detected by electrophoretic mobility shift assay (EMSA). Exposure to this regimen of cigarette smoke induced peribronchial and perivascular lymphocytic aggregates and parenchymal accumulation of macrophages in rats. EMSA demonstrated that smoke exposure enhanced NF-κB activation in rats’ alveolar macrophages (AMs). Compared with the control group, smoke exposure induced a notable increase in TNF-α and IL-1β in BALF, lung tissues, and a decrease of β₂-AR expression of AMs. The expression of β₂-AR from AMs was inversely correlated with TNF-α and IL-1β levels of BALF. These data demonstrated that chronic smoke-triggered lung inflammation was accompanied by down-regulation of β₂-AR in rat lungs’ AMs.

• β2-Adrenergic receptor
• alveolar macrophages
• cigarette smoke
• inflammation

Acknowledgements

The authors would like to thank Dr. Laura Heraty for language revision.

Declaration of interest

The authors report that they have no conflicts of interest. The authors wish to thank the National Natural Science Foundation Council (China) and Foundation of Peking University Third Hospital for the funding of this work