2.1.3 The ARA receptor
A2AR protein is considered to be an important mediator of inflammation and immune response. In monocytes, caffeine reduces the secretion of TNF-α by monocytes by blocking adenosine receptors50. Animal experiments found that mouse TNF-α, IL-1β, and phosphorylated-NF-κB proteins were positively correlated with A2AR proteins. Caffeine, as an A2A receptor antagonist, has been shown to reduce pulmonary inflammatory infiltration and apoptosis and promote the development of type II alveolar epithelial cells44. In LPS/ATP-induced THP-1 macrophages, caffeine was shown to inhibit the ROS-mediated activation of NLRP3 inflammatory vesicles and reduced the secretion of IL-1β and IL-18 in THP-1 macrophages by decreasing the gene transcription and protein expression of A2AR43. In addition,caffeine antagonism of A2AR was shown to modulate neutrophil production by inflammatory factors and reduce the inflammatory response to oxidative stress51.