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.