scholarly journals Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Davide Di Paola ◽  
Sabrina Natale ◽  
Carmelo Iaria ◽  
Marika Cordaro ◽  
Rosalia Crupi ◽  
...  
Keyword(s):  
Er Stress ◽  
Protective Action ◽  
Mucus Production ◽  
Stress Genes ◽  
Zebrafish Larvae ◽  
Genes Expression ◽  
Repetitive Exposure ◽  
Inflammatory Bowel ◽  
Stress Related Genes ◽  
Gut Damage

IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

scholarly journals Emc3 maintains intestinal homeostasis by preserving secretory lineages

2021 ◽  
Author(s):  
Meina Huang ◽  
Li Yang ◽  
Ning Jiang ◽  
Quanhui Dai ◽  
Runsheng Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Dominant Role ◽  
Paneth Cell ◽  
Intestinal Barrier ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Intestinal Barrier Function ◽  
Endoplasmic Reticulum Membrane ◽  
Mucus Production

AbstractIntestinal exocrine secretory lineages, including goblet cells and Paneth cells, provide vital innate host defense to pathogens. However, how these cells are specified and maintained to ensure intestinal barrier function remains poorly defined. Here we show that endoplasmic reticulum membrane protein complex subunit 3 (Emc3) is essential for differentiation and function of exocrine secretory lineages. Deletion of Emc3 in intestinal epithelium decreases mucus production by goblet cells and Paneth cell population, along with gut microbial dysbiosis, which result in spontaneous inflammation and increased susceptibility to DSS-induced colitis. Moreover, Emc3 deletion impairs stem cell niche function of Paneth cells, thus resulting in intestinal organoid culture failure. Mechanistically, Emc3 deficiency leads to increased endoplasmic reticulum (ER) stress. Mitigating ER stress with tauroursodeoxycholate acid alleviates secretory dysfunction and restores organoid formation. Our study identifies a dominant role of Emc3 in maintaining intestinal mucosal homeostasis.

scholarly journals Inflammatory Bowel Diseases: Host-Microbial-Environmental Interactions in Dysbiosis

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 13
Author(s):  
Catherine Colquhoun ◽  
Michelle Duncan ◽  
George Grant
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Early Life ◽  
Secretory Iga ◽  
Mucus Production ◽  
Functional Changes ◽  
Environmental Interactions ◽  
Intestinal Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Abundance And Diversity

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are world-wide health problems in which intestinal dysbiosis or adverse functional changes in the microbiome are causative or exacerbating factors. The reduced abundance and diversity of the microbiome may be a result of a lack of exposure to vital commensal microbes or overexposure to competitive pathobionts during early life. Alternatively, many commensal bacteria may not find a suitable intestinal niche or fail to proliferate or function in a protective/competitive manner if they do colonize. Bacteria express a range of factors, such as fimbriae, flagella, and secretory compounds that enable them to attach to the gut, modulate metabolism, and outcompete other species. However, the host also releases factors, such as secretory IgA, antimicrobial factors, hormones, and mucins, which can prevent or regulate bacterial interactions with the gut or disable the bacterium. The delicate balance between these competing host and bacteria factors dictates whether a bacterium can colonize, proliferate or function in the intestine. Impaired functioning of NOD2 in Paneth cells and disrupted colonic mucus production are exacerbating features of CD and UC, respectively, that contribute to dysbiosis. This review evaluates the roles of these and other the host, bacterial and environmental factors in inflammatory bowel diseases.

Enteroids Derived From Inflammatory Bowel Disease Patients Display Dysregulated Endoplasmic Reticulum Stress Pathways, Leading to Differential Inflammatory Responses and Dendritic Cell Maturation

2019 ◽  
Vol 14 (7) ◽  
pp. 948-961 ◽  
Author(s):  
William D Rees ◽  
Martin Stahl ◽  
Kevan Jacobson ◽  
Brian Bressler ◽  
Laura M Sly ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Bowel Disease ◽  
Inflammatory Responses ◽  
Human Colon ◽  
Intestinal Epithelial ◽  
Stress Changes ◽  
Inflammatory Bowel ◽  
Stress Pathway

Abstract Background and Aims Endoplasmic reticulum [ER] stress in intestinal epithelial cells [IECs] contributes to the pathogenesis of inflammatory bowel disease [IBD]. We hypothesized that ER stress changes innate signalling in human IECs, augmenting toll-like receptor [TLR] responses and inducing pro-inflammatory changes in underlying dendritic cells [DCs]. Methods Caco-2 cells and primary human colon-derived enteroid monolayers were exposed to ATP [control stressor] or thapsigargin [Tg] [ER stress inducer], and were stimulated with the TLR5 agonist flagellin. Cytokine release was measured by an enzyme immunoassay. ER stress markers CHOP, GRP78 and XBP1s/u were measured via quantitative PCR and Western blot. Monocyte-derived DCs [moDCs] were cultured with the IEC supernatants and their activation state was measured. Responses from enteroids derived from IBD patients and healthy control participants were compared. Results ER stress enhanced flagellin-induced IL-8 release from Caco-2 cells and enteroids. Moreover, conditioned media activated DCs to become pro-inflammatory, with increased expression of CD80, CD86, MHCII, IL-6, IL-15 and IL-12p70 and decreased expression of CD103 and IL-10. Flagellin-induced IL-8 production correlated with DC activation, suggesting a common stress pathway. Moreover, there were distinct differences in cytokine expression and basal ER stress between IBD and healthy subject-derived enteroid monolayers, suggesting a dysregulated ER stress pathway in IBD-derived enteroids. Conclusions Cellular stress enhances TLR5 responses in IECs, leading to increased DC activation, indicating a previously unknown mechanistic link between epithelial ER stress and immune activation in IBD. Furthermore, dysregulated ER stress may be propagated from the intestinal epithelial stem cell niche in IBD patients.

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