P071 G protein-coupled receptor 30 expression in inflammatory bowel disease patients

Abstract

Background: G protein-coupled receptor 30 (GPR30) is a novel estrogen receptor that mediates estrogenic effects on the human endothelial cells which plays an important role in the inflammatory response. It has been postulated that in inflammatory bowel diseases (IBD) GPR30 blocks the immunological pathway dependent on pro-inflammatory proteins, such as intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). However, little is known about the protein expression of GPR30 and its role in IBD. Therefore, the aim of this pilot study was to determine whether GPR30 is expressed in colonic tissue of IBD patients and if so, whether the GPR30 protein expression differs between non-IBD and IBD patients. Methods: 17 patients were enrolled in our study, 10 women with a mean age of 39±18 yrs and 7 men with a mean age of 33±13 yrs. Controls consisted of 4 healthy non-IBD patients. In each subject two biopsies were taken from different colonic locations in Crohn’s disease (CD;n = 9), ulcerative colitis (UC;n = 3) and control patients (n = 4). In IBD patients biopsies both from all endoscopically inflamed and non-inflamed areas were drawn and confirmed in histopatological examination. The GPR30 protein content was detected using immunoenzymatic (Western blot) method with specific primary antibodies against GPR30 protein. Three types of samples were analyzed: control, non-inflamed and inflamed colon biopsies from IBD patients. Each assay was performed in triplicates. Results: In our study the higher protein content of colonic GPR30 in men than in women was recorded (1.97±1.24 vs. 0.83±0.64; p = 0.026). Interestingly, an up-regulation of GPR30 protein level in CD and UC patients when compared to control was observed (1.65±1.1 vs. 0.47±0.11; p = 0.033). The upregulation of GPR30 in IBD patients was sex-independent. The comparison of the GPR30 protein level in the inflamed vs. noninflamed and non-inflamed tissue samples from the same IBD patient indicated that there is a tendency toward lower GPR30 protein content in inflamed than in non-inflamed tissue. The reduced level of GPR30 in inflamed tissue in CD and UC patients was independent from sex and intestinal location. Conclusions: GPR30 protein is detectable in colonic tissue of IBD patients. The non-inflamed areas of colonic tissue of IBD patients are characterized by higher protein level of GPR30. The up-regulation of GPR30 in non-inflamed areas seems to be independent from sex and lesions location. Therefore, we speculate that GPR30 can play a role in inhibition of inflammatory process in IBD patients and may affect the level of disease severity as well, as the response to treatment. The GPR30 receptors may become an attractive target for novel drugs in the treatment of IBD. P072 GLPG0634, the first selective JAK1 inhibitor, shows strong activity in the mouse DSS-colitis model