IL-6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

摘要

The aim of the present study was to investigate the effect of the IL-6/STAT3 signaling pathway on intestinal epithelial barrier injury in patients with ulcerative colitis (UC). Fifty-two patients with UC and 21 healthy subjects were recruited. The expression level of IL-6 in plasma was determined by ELISA. Normal human colon mucosal epithelial NCM460 cells were treated with IL-6 or plasma from the patients with UC. Then, the transepithelial electrical resistance value, fluorescein yellow permeability and zonulin release were evaluated. Using reverse transcription-quantitative (q)PCR and western blotting, claudin (CLDN) 1 and CLDN2 expression levels were analyzed. Furthermore, western blotting was used to detect phosphorylation of STAT3. Chromatin immunoprecipitation-qPCR was performed to investigate the enrichment of H3K27ac in the promoter regions of CLDN1 and CLDN2. The present study revealed that IL-6 content was elevated in the plasma from patients with UC and increased with the progression of the disease. IL-6 was also observed to induce intestinal epithelial cell barrier injury and regulate barrier function by influencing the expression of tight junction-related proteins, as well as STAT3. The IL-6/STAT3 signaling pathway regulated transcription of CLDN1 and CLDN2 by affecting the enrichment of histone H3K27ac in their promoter regions. Thus, the significantly increased expression level of IL-6 in the peripheral blood of patients with UC indicates a positive association with the development of UC. Furthermore, the IL-6/STAT3 signaling pathway influences the function of the intestinal barrier by affecting the H3K27ac level in intestinal epithelial cells.