scholarly journals Endoplasmic Reticulum Stress and Intestinal Inflammation: A Perilous Union

2020 ◽  
Vol 11 ◽  
Author(s):  
Sanchez Preethi Eugene ◽  
Vadde Sudhakar Reddy ◽  
Jamma Trinath
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Er Stress ◽  
Lamina Propria ◽  
Immune Cells ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Pharmacological Intervention ◽  
Intestinal Epithelial ◽  
Exogenous Origin

The intestinal tract encompasses the largest mucosal surface fortified with a fine layer of intestinal epithelial cells along with highly sophisticated network of the lamina propria immune cells that are indispensable to sustain gut homeostasis. However, it can be challenging to uphold homeostasis when these cells in the intestine are perpetually exposed to insults of both endogenous and exogenous origin. The complex networking and dynamic microenvironment in the intestine demand highly functional cells ultimately burdening the endoplasmic reticulum (ER) leading to ER stress. Unresolved ER stress is one of the primary contributors to the pathogenesis of inflammatory bowel diseases (IBD). Studies also suggest that ER stress can be the primary cause of inflammation and/or the consequence of inflammation. Therefore, understanding the patterns of expression of ER stress regulators and deciphering the intricate interplay between ER stress and inflammatory pathways in intestinal epithelial cells in association with lamina propria immune cells contribute toward the development of novel therapies to tackle IBD. This review provides imperative insights into the molecular markers involved in the pathogenesis of IBD by potentiating ER stress and inflammation and briefly describes the potential pharmacological intervention strategies to mitigate ER stress and IBD. In addition, genetic mutations in the biomarkers contributing to abnormalities in the ER stress signaling pathways further emphasizes the relevance of biomarkers in potential treatment for IBD.

scholarly journals Crosstalk Between Nuclear Glucose-Regulated Protein 78 and Tumor Protein 53 Contributes to the Lipopolysaccharide Aggravated Apoptosis of Endoplasmic Reticulum Stress-Responsive Porcine Intestinal Epithelial Cells

2018 ◽  
Vol 48 (6) ◽  
pp. 2441-2455 ◽  
Author(s):  
Qian Jiang ◽  
Gang Liu ◽  
Jiashun Chen ◽  
Kang Yao ◽  
Yulong Yin
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Endoplasmic Reticulum Stress ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Gram Negative ◽  
Rna Transfection ◽  
Glucose Regulated Protein

Background/Aims: Lipopolysaccharides (LPSs) act as virulence factors that trigger intestinal inflammation and thereby compromise the production of pigs worldwide. Intestinal diseases and dysfunction have been attributed to endoplasmic reticulum stress (ERS) and the subsequent apoptosis of intestinal epithelial cells. Therefore It is important to explore whether LPSs aggravate ERS-mediated apoptosis of intestinal epithelial cells. Methods: ERS and inflammation models were established in porcine cell line J2 (IPEC-J2) and the cells were treated with tunicamycin or LPS at specific times. The expression of marker proteins was determined by western blot and immunofluorescence. Possible crosstalk between proteins was analyzed by co-immunoprecipitation. Small interfering RNA transfection was employed to verify the mechanisms. Results: We found that Escherichia coli-derived LPS aggravated ERS and ERS-mediated apoptosis in ERS-responsive IPEC-J2 cells. The crosstalk between nuclear glucose-regulated protein 78 (GRP78) and tumor protein 53 (p53) was verified to trigger this LPS-aggravated apoptosis of ERS-responsive intestinal cells. Conclusion: This novel finding implies that intestinal malfunctions might solely originate from the effects of Gram-negative bacteria on ERS-responsive intestinal cells. The regulation of ERS signaling (especially the crosstalk between nuclear GRP78 and p53) in ERS-responsive/rapidly growing intestines may help intestinal cells survive from Gram-negative bacterial infections.

scholarly journals Endoplasmic Reticulum Stress–Mediated Autophagy and Apoptosis Alleviate Dietary Fat–Induced Triglyceride Accumulation in the Intestine and in Isolated Intestinal Epithelial Cells of Yellow Catfish

2019 ◽  
Vol 149 (10) ◽  
pp. 1732-1741 ◽  
Author(s):  
Shi-Cheng Ling ◽  
Kun Wu ◽  
Dian-Guang Zhang ◽  
Zhi Luo
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Epithelial Cells ◽  
Er Stress ◽  
Dietary Fat ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Yellow Catfish ◽  
Triglyceride Accumulation ◽  
Induced Changes

ABSTRACTBackgroundThe intestine is the main organ for absorbing dietary fat. High dietary lipid intake leads to fat deposition in the intestine and adversely influences fat absorption and health, but the underlying mechanism is unknown.ObjectivesWe used yellow catfish and their isolated intestinal epithelial cells to test the hypothesis that endoplasmic reticulum (ER) stress, autophagy, and apoptosis mediate fat-induced changes in lipid metabolism.MethodsMale and female yellow catfish (weight: 3.79 ± 0.16 g; age: 3 mo) were fed diets containing lipid at 6.98% (low-fat diet; LFD), 11.3% (middle-fat diet; MFD), or 15.4% (high-fat diet; HFD) (by weight) for 8 wk. Each dietary group had 3 replicates, 30 fish per replicate. Their intestinal epithelial cells were isolated and incubated for 24 h in control solution or various concentrations of fatty acids (FAs) with or without 2-h pretreatment with an inhibitor [3-methyladenine (3-MA), 4-phenyl butyric acid (4-PBA), or Ac-DVED-CHO (AC)]. Triglyceride (TG) contents, genes, and enzymes involved in lipid metabolism, ER stress, autophagy, and apoptosis were determined in intestinal tissue and cells; immunoblotting, BODIPY 493/503 staining, ultrastructural observation, and the detection of autophagic and apoptotic vesicles were performed on intestinal cells.ResultsCompared with the LFD and MFD, the HFD increased intestinal TG content by 120–226%, activities of lipogenic enzymes by 19.0–245%, expression of genes related to lipogenesis (0.77–8.4-fold), lipolysis (0.36–6.0-fold), FA transport proteins (0.79–1.7-fold), ER stress (0.55–7.5-fold), autophagy (0.56–4.2-fold), and apoptosis (0.80–5.2-fold). Using isolated intestinal epithelial cells and inhibitors (4-PBA, 3-MA, and AC), we found that ER stress mediated FA-induced activation of autophagy (11.0–50.1%) and apoptosis (10.4–32.0%), and lipophagy and apoptosis mediated FA-induced lipolysis (3.40–41.6%).ConclusionsAn HFD upregulated lipogenesis, lipolysis, and FA transport, induced ER stress, and activated autophagy and apoptosis. ER stress, autophagy, and apoptosis play important regulatory roles in fat-induced changes in lipid metabolism in the intestine and intestinal epithelial cells of yellow catfish.

Analysis of the role of the endoplasmic reticulum stress response-related molecule CHOP in intestinal epithelial cells

Impact ◽  
2021 ◽  
Vol 2021 (6) ◽  
pp. 18-20
Author(s):  
Yosuke Shimodaira
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Epithelial Cells ◽  
Er Stress ◽  
Intestinal Epithelial Cells ◽  
Bloody Stool ◽  
Intestinal Epithelial ◽  
Stomach Pain ◽  
Intestinal Immune System

Inflammatory bowel diseases (IBDs) include ulcerative colitis and Crohn's disease. The symptoms experienced by people with IBD include diarrhea, bloody stool, extreme tiredness, weight loss and stomach pain. IBD is on the rise globally and it is unknown why. There is no existing cure for the condition and treatments are not always successful. In the quest to find a cure for IBD, researchers are investigating the mechanisms of the disease. Dr Yosuke Shimodaira, Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Japan, is seeking to understand more about the mechanisms involved in the development of the disease. A key part of this research is autophagy and Shimodaira and the team are working to shed light on why endoplasmic reticulum (ER) stress in the intestinal epithelial cells induces autophagy and the role this might play in the development of IBD. A key learning for the team was that C/EBP-homologous protein (CHOP) is involved in the ER stress response. An important focus for the researchers is on the role played by CHOP in intestinal epithelial cells in vivo and its involvement in the pathophysiology of IBD. Shimodaira and the team plan to conduct experiments using mice and patients samples to analyse these fundamental mechanism in intestinal homeostasis. This will enable them to determine whether CHOP plays a role in vivo and how CHOP affect intestinal immune system.

scholarly journals Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation

2017 ◽  
Vol 214 (10) ◽  
pp. 2985-2997 ◽  
Author(s):  
Shuhei Hosomi ◽  
Joep Grootjans ◽  
Markus Tschurtschenthaler ◽  
Niklas Krupka ◽  
Juan D. Matute ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Er Stress ◽  
Intestinal Inflammation ◽  
Binding Protein ◽  
Lymphoid Cells ◽  
Intestinal Epithelial ◽  
Related Transcription Factor ◽  
Factor C

Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box–binding protein 1 (Xbp1), an unfolded protein response–related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1ΔIEC) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)–like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress–related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1+ cells also significantly improved enteritis, whereas enteritis was not ameliorated in Recombinase activating gene 1−/−;Xbp1ΔIEC mice. These experiments reveal innate immune sensing of ER stress in IECs as an important mechanism of intestinal inflammation.

Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Fungal Protein ◽  
Fungal Immunomodulatory Protein

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...

Sign in / Sign up

Export Citation Format

Share Document