Shining a Light on Barrier Function

Infliximab treatment of postoperative ulcers in Crohn's disease: to inject or not to inject—that is the question

The Use of Intestinal Ultrasound in Ulcerative Colitis—More Than a Mucosal Disease?

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Computer-Aided Diagnosis With Monochromatic Light Endoscopy for Scoring Histologic Remission in Ulcerative Colitis

Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases

SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): An International Multidisciplinary Consensus

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics

Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

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

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review