Regulation of mast cell degranulation and intestinal permeability by the corticotropin-releasing factor (CRF) system

Stress-related GI diseases, such as IBS, are characterized by increased mast cell numbers and heightened release of mast cell mediators (e.g. histamine, proteases, and TNF). Released mast cell products can impair intestinal barrier function and activate sensory neurons, which contribute to clinical signs of abdominal pain and diarrhea.

While the role of mast cells and their products in stress-induced intestinal disorders is known, very little is known about how mast cells are regulated during the stress response.

Previous work from our lab (Moeser 2006; Smith et al 2010; Overman et al 2010) and others (Wallon et al., 2008; Cao et al. 2006; Santos et al. 1996) have shown that a key stress response system that is linked with activation of intestinal mast cells and the CRF system. The CRF system is composed of two G-protein-coupled CRF receptors, CRF1 and CRF2, and their ligands CRF, and the related family of Urocortins (Ucn1-3). Precisely how the CRF system interacts with mast cells to provoke mast cell activation is poorly understood. A current area of research focus in this laboratory is to investigate how mast cells are regulated in response to psychological and immunological stressors via the CRF system.