Urocortin 1 and Urocortin 2 induce macrophage apoptosis via CRFR2

Abstract
Macrophages undergo apoptosis as a mechanism of regulating their activation and the inflammatory reaction. Macrophages express the Corticotropin‐Releasing Factor Receptor‐2 (CRFR2) the endogenous agonists of which, the urocortins, are also present at the site of inflammation. We have found that urocortins induced macrophage apoptosis in a dose‐ and time‐dependent manner via CRFR2. In contrast to lipopolysaccharide (LPS)‐induced apoptosis, the pro‐apoptosis pathway activated by urocortins involved the pro‐apoptotic Bax and Bad proteins and not nitric oxide, JNK and p38MAPK characteristic of LPS. In conclusion, our data suggest that endogenous CRFR2 ligands exert an anti‐inflammatory effect via induction of macrophage apoptosis.