Endogenous noradrenaline (NA) has multiple bioactive functions and, in the 
central nervous system (CNS), has been implicated in modulating 
neuroinflammation via β-adrenergic receptors (β-ARs). Microglia, resident 
macrophages in the CNS, have a central role in the brain immune system and have 
been reported to be activated by NA. However, intracellular signaling mechanisms 
of the AR-mediated proinflammatory responses of microglia are not fully 
understood. Using a rapid and stable in vitro reporter assay system to evaluate 
IL-1β production in microglial BV2 cells, we found that NA and the β-AR agonist 
isoproterenol upregulated the IL-1β reporter activity. This effect was 
suppressed by β-AR antagonists. We further examined the involvement of EPAC 
(exchange protein directly activated by cAMP) and TPL2 (tumor progression locus 
2, MAP3K8) and found that inhibitors for EPAC and TPL2 reduced AR 
agonist-induced IL-1β reporter activity. These inhibitors also suppressed 
NA-induced endogenous Il1b mRNA expression and IL-1β protein production. Our 
results suggest that EPAC and TPL2 are involved in β-AR-mediated IL-1β 
production in microglial cells, and extend our understanding of its 
intracellular signaling mechanism.