Clock-controlled StAR’s expression and corticosterone production contribute to the endotoxemia immune response

Previously, we reported Per2 m/m mice displayed a down-regulated circadian immune response to lipopolysaccharide (LPS) challenge. However, the mediators between Per2 and immune function and their underlying mechanisms remain unclear.

In this study, serum corticosterone (CORT), a hormone which played a crucial role in immune suppression, was found to be significantly increased in Per2 m/m mice compared with the one in wild-type mice following LPS administration at ZT3 and ZT8. The elevated level of serum CORT was correlated with their higher survival rate, which could be further suppressed by glucocorticoid receptor antagonist. Expression of StAR, a rate-limiting enzyme in CORT synthesis, as well as the expression of core clock genes ( Clock/Bmal1) , was more strongly induced and longer lasting in Per2 m/m mice in contrast to the ones in control mice after LPS injection.