Caspase 1 activation can be induced by oxidative stress, which leads to the release of the proinflammatory
cytokines IL1β and
IL18 in myeloid cells and a potentially damaging inflammatory response. However, little is known about the role of
caspase 1 in non-immune cells, such as hepatocytes, that express and activate the
inflammasome but do not produce a significant amount of IL1β/
IL18. Here we demonstrate that
caspase 1 activation protects against cell death after redox stress induced by
hypoxia/reoxygenation in hepatocytes. Mechanistically, we show that
caspase 1 reduces mitochondrial respiration and
reactive oxygen species by increasing mitochondrial autophagy and subsequent clearance of mitochondria in hepatocytes after
hypoxia/reoxygenation.
Caspase 1 increases autophagic flux through up-regulating autophagy initiator
beclin 1 during redox stress and is an important cell survival factor in hepatocytes. We find that during
hemorrhagic shock with
resuscitation, an in vivo mouse model associated with severe hepatic redox stress,
caspase 1 activation is also protective against liver injury and excessive oxidative stress through the up-regulation of
beclin 1. Our findings suggest an alternative role for
caspase 1 activation in promoting adaptive responses to oxidative stress and, more specifically, in limiting
reactive oxygen species production and damage in cells and tissues where IL1β/
IL18 are not highly expressed.