Endoplasmic reticulum stress in gut inflammation: Implications for ulcerative colitis and Crohn’s disease

Table 1 Differences in ulcerative colitis and Crohn’s disease between the three pathways

Access	Mechanism of action	UC	CD
PERK	Inhibiting the start of mRNA translation reduces protein synthesis, whereas activating ATF4 increases the expression of antioxidant enzymes	PERK affects the integrity of the mucosal barrier and the proper functioning of intestinal epithelial cells. It also changes the course of inflammation by controlling the levels of pro- and anti-inflammatory cytokines	PERK in CD affects disease progression primarily by modulating the activity of immune cells, including T cells and macrophages, that participate in the inflammatory response
IRE1	It facilitates mRNA splicing, augments protein folding ability, and supports ER adaptation	The mucosal layer of the colon is the only area where UC occurs, with IRE1 activation and its subsequent effects primarily localized there and associated with Th2 cell-mediated immune responses	CD can affect any part of the digestive tract, causing lesions to spread out in different areas and mostly triggering a Th1 and Th17 immune response
ATF6	The regulation of ER related gene expression and enhancement of protein folding capability are being discussed	ATF6 is a key player in fixing the mucosal layer and keeping the intestinal barrier working well in UC. It does this by improving the growth and differentiation of epithelial cells	A discontinuous lesion characterizes tissue damage in CD, and ATF6 frequently plays a role in aberrant tissue repair as well as the formation of fistulas and strictures

PERK: Protein kinase RNA-like endoplasmic reticulum kinase; IRE1: Inositol-requiring enzyme 1; ATF6: Activating transcription factor 6; ATF4: Activating transcription factor 4; ER: Endoplasmic reticulum; UC: Ulcerative colitis; CD: Crohn’s disease; Th2: T helper 2 cell; Th17: T helper cell 17; Th1: T helper cell 1.

Table 2 Commonly used drugs for the treatment of inflammatory bowel disease

Drugs	Mechanism of action	Clinical application	Adverse reaction
Mesalamine	Decreased synthesis of prostaglandins and leukotrienes	Patients with mild to moderate UC should maintain remission	Gastrointestinal upset, headaches, and kidney damage
Prednisone	It reduces leukocyte migration and suppresses the immune response	Short-term induced remission in moderately to severely active CD and UC is possible	Weight gain osteoporosis diabetes
Budesonide	Inhibits multiple inflammatory mediators	There was an induced remission of moderate to mild CD	Gastrointestinal distress and mild hypertension
Azathioprine	It inhibits purine synthesis and reduces leukocyte activation	We maintain the remission of CD and UC while reducing our reliance on hormones	Bone marrow suppression, hepatotoxicity, and nausea
Infliximab	Anti-TNF-α inhibits inflammatory response	Both of these therapies are either ineffective or poorly tolerated	Infusion reactions and drug resistance
Ustekinumab	Anti-IL-12/23 inhibits activation of Th1 and Th17 cells	CD and UC are moderately to severely active	Injection site reactions: Risk of infection

IL: Interleukin; TNF: Tumor necrosis factor; UC: Ulcerative colitis; CD: Crohn’s disease; Th17: T helper cell 17; Th1: T helper cell 1.