Expression of corticotropin releasing factor receptor type 1 (CRF1) in the human gastrointestinal tract and upregulation in the colonic mucosa in patients with ulcerative colitis

Abstract

Brain corticotropin-releasing factor (CRF) acting on CRF receptor type 1 (CRF1) is a main signaling pathway in the stress response. CRF is also produced in a variety of peripheral sites and acts locally as a proinflammatory mediator. We investigated CRF1 mRNA expression in the human gastrointestinal tract, and localized CRF1 immunoreactive cells in the colonic mucosa of healthy subjects and patients with ulcerative colitis (UC). In 4 male healthy subjects (24–29 years), CRF1 transcript was detected by RT-PCR throughout the gastrointestinal tract with the highest levels in the ileum and rectum and the lowest level in the colon. Immunohistochemistry on whole thickness sigmoid colon sections showed that CRF1 was localized in the lamina propria and epithelial cells and enteric neurons. In sigmoid colonic biopsies, immunohistochemically double-labeled cells with CRF1 and CD163, a marker for macrophages, represent 79% of total CRF1 immunoreactive (IR) cells in healthy subjects. In 10 UC patients, the total number of CRF1 IR cells and CRF1/CD163 double-labeled macrophages was increased by 4.2 and 4.0 folds respectively compared to healthy subjects. These findings indicate that CRF1 is distributed throughout the GI tract of healthy human subjects. The increase of CRF1 IR cells prominently in macrophages of the sigmoid colonic mucosa of UC patients provides anatomical support for a role of CRF1 signaling in modulating the immune-inflammatory process of UC.