Hypoxia has been shown to promote
inflammation, including the release of proinflammatory
cytokines, but it is poorly investigated how
hypoxia directly affects
inflammasome signaling pathways. To explore whether hypoxic stress modulates
inflammasome activity, we examined the effect of
cobalt chloride (CoCl2)-induced
hypoxia on caspase-1 activation in primary mixed glial cultures of the neonatal mouse brain. Unexpectedly,
hypoxia induced by
oxygen-
glucose deprivation or CoCl2 treatment failed to activate caspase-1 in microglial BV-2 cells and primary mixed glial cultures. Of particular interest, CoCl2-induced hypoxic condition considerably inhibited NLRP3-dependent caspase-1 activation in mixed glial cells, but not in bone marrow-derived macrophages. CoCl2-mediated inhibition of NLRP3
inflammasome activity was also observed in the isolated brain microglial cells, but CoCl2 did not affect
poly dA:dT-triggered AIM2
inflammasome activity in mixed glial cells. Our results collectively demonstrate that CoCl2-induced
hypoxia may negatively regulate NLRP3
inflammasome signaling in brain glial cells, but its physiological significance remains to be determined.