Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway
Xijuan Wang,
Shuai Lv,
Jianwei Sun,
Meihui Zhang,
Lei Zhang,
Yan Sun,
Ziyan Zhao,
Dandan Wang,
Xinjing Zhao,
Jiajie Zhang
Affiliations
Xijuan Wang
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Shuai Lv
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China
Jianwei Sun
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Meihui Zhang
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Lei Zhang
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Yan Sun
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Ziyan Zhao
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Dandan Wang
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Xinjing Zhao
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Jiajie Zhang
Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of China
Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 μM caffeine), antagonist (5 μM ZM241385), agonist (5 μM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. A2AR may serve as a promising therapeutic target for BPD in prematurity.
