Endoplasmic Reticulum Stress-activated C/EBP Homologous Protein Enhances Nuclear Factor-κB Signals via Repression of Peroxisome Proliferator-activated Receptor γ

摘要: Endoplasmic reticulum (ER) stress is a causative factor of inflammatory bowel diseases. ER mediators, including CCAAT enhancer-binding protein (C/EBP) homologous (CHOP), are elevated in intestinal epithelia from patients with The present study arose the question how chemical and CHOP were associated nuclear factor-κB (NF-κB)-mediated epithelial response. In human cell culture model, stresses induced proinflammatory cytokine interleukin-8 (IL-8) expression translocation protein. was positively involved ER-activated IL-8 production negatively peroxisome proliferator-activated receptor γ (PPARγ). stress-induced enhanced by NF-κB activation that regulated PPARγ. Mechanistically, suppressed PPARγ transcription sequestering C/EBPβ limiting availability binding to promoter. Due CHOP-mediated regulation action, can enhance maintain an increased level cells. contrast, counteracting regulator gut response through attenuation activation. collective results support view balances between crucial for homeostasis, disruption these mucosal etiologically affect progress