Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease.
The unfolded protein response as a consequence of endoplasmic reticulum (ER) stress has recently been implicated as a novel mechanism that may lead to inflammatory bowel disease (IBD). Impairment of proper ER stress resolution in highly secretory Paneth and, to a lesser extent, goblet cells within the epithelium can primarily lead to intestinal inflammation. An inability to manage ER stress may not only be a primary originator of intestinal inflammation as exemplified by genetic polymorphisms in XBP1 that are associated with IBD but also a perpetuator of inflammation when ER stress is induced secondarily to inflammatory mediators or microbial factors. Furthermore, ER stress pathways may interact with other processes that lead to IBD, notably autophagy.
Kaser
Arthur
A
Department of Medicine II (Gastroenterology and Hepatology), Innsbruck Medical University, Innsbruck, Austria.
Blumberg
Richard S
RS
D000818:Animals; D001343:Autophagy / Q000276:immunology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D020397:Goblet Cells / Q000276:immunology / Q000648:ultrastructure; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D019879:Paneth Cells / Q000276:immunology / Q000648:ultrastructure; D011110:Polymorphism, Genetic; D017510:Protein Folding; D000071701:Regulatory Factor X Transcription Factors; D013312:Stress, Physiological / Q000276:immunology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human