Role of autophagy in the pathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. Recently, some studies provided strong evidence that the process of autophagy affects several aspects of mucosal immune responses. Autophagy is a cellular stress response that plays key roles in physiological processes, such as innate and adaptive immunity, adaptation to starvation, degradation of aberrant proteins or organelles, antimicrobial defense, and protein secretion. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including IBD. Autophagy plays multiple roles in IBD pathogenesis by altering processes that include intracellular bacterial killing, antimicrobial peptide secretion by Paneth cells, goblet cell function, proinflammatory cytokine production by macrophages, antigen presentation by dendritic cells, and the endoplasmic reticulum stress response in enterocytes. Recent studies have identified susceptibility genes involved in autophagy, such as NOD2, ATG16L1, and IRGM, and active research is ongoing all over the world. The aim of this review is a systematic appraisal of the current literature to provide a better understanding of the role of autophagy in the pathogenesis of IBD. Understanding these mechanisms will bring about new strategies for the treatment and prevention of IBD.

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

“…Conversely, in QCD no changes were observed in BAX, Beclin‐1, and Bcl2, whereas Bcl‐xL was increased and BNIP3 was decreased. ICD were characterized by increments of BAX, Bcl‐xL, and Bcl2, and decreased level of BNIP3, whereas Beclin‐1 was unchanged …”

“…ICD were characterized by increments of BAX, Bcl-xL, and Bcl2, and decreased level of BNIP3, whereas Beclin-1 was unchanged. [42]…”

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

“…Ulcerative colitis (UC) is an idiopathic chronic inflammatory bowel disease that its pathogenesis involves complex interactions between genes and environment (de Souza, Fiocchi, & Iliopoulos, 2017;Iida, Onodera, & Nakase, 2017;Kim & Cheon, 2017). Although the precise pathologic mechanism during UC is still controversial, increasing evidences from experiments and clinical patients indicate that excessive inflammation and abnormal immunity are crucial to the pathogenesis of UC (Alexander, Targan, & Elson, 2014;Park, Peyrin-Biroulet, Eisenhut, & Shin, 2017).…”

Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell

“…UC is a chronic inflammatory disorder of the gastrointestinal tract [31]. The abnormal immune response or destruction of normal immune regulation is an important part of the pathogenesis of UC [32,33]. Overproduction of proinflammatory cytokines can produce chemotactic effects on inflammatory cells, including neutrophils, to attract them into intestinal lesions, resulting in intestinal mucosal edema, increased permeability of the intestinal mucosa and an exacerbated intestinal reaction, eventually leading to the occurrence of UC [7,34].…”