Prolyl isomerase pin1 protects mice from endotoxin shock.

Abstract

Prolyl isomerase Pin1 may be involved in innate immunity against microbial infection, but the mechanism how Pin1 controls the innate immunity is poorly understood.Injection of lipopolysaccharide (LPS) into the mice induces inflammatory pulmonary disorder and sometimes the serious damages lead to death. Comparing to the wild-type (WT) mice, the Pin1⁻/⁻ mice showed more serious damages in lung and the lower survival rate after the LPS injection. We compared the levels of typical inflammatory cytokines. Pin1⁻/⁻ mice overreacted to the LPS injection to produce inflammatory cytokines, especially IL-6 more than WT mice. We showed that Pin1 binds phosphorylated PU.1 and they localize together in a nucleus. These results suggest that Pin1 controls the transcriptional activity of PU.1 and suppresses overreaction of macrophage that causes serious damages in lung.Pin1 may protect the mice from serious inflammation by LPS injection by attenuating the increase of IL-6 transcription of the mouse macrophages.