Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation in the intestine. Given their role in regulation of inflammation, long‐chain n‐3 polyunsaturated fatty acids (PUFAs) represent a potential supplementary therapeutic approach to current drug regimens used for IBD. Mechanistically, there is ample evidence for an anti‐inflammatory and pro‐resolution effect of long‐chain n‐3 PUFAs after they incorporate into cell membrane phospholipids. They disrupt membrane rafts and when released from the membrane suppress inflammatory signaling by activating PPAR‐γ and free fatty acid receptor 4; furthermore, they shift the lipid mediator profile from pro‐inflammatory eicosanoids to specialized pro‐resolving mediators. The allocation of long‐chain n‐3 PUFAs also leads to a higher microbiome diversity in the gut, increases short‐chain fatty acid‐producing bacteria, and improves intestinal barrier function by sealing epithelial tight junctions. In line with these mechanistic studies, most epidemiological studies support a beneficial effect of long‐chain n‐3 PUFAs intake on reducing the incidence of IBD. However, the results from intervention trials on the prevention of relapse in IBD patients show no or only a marginal effect of long‐chain n‐3 PUFAs supplementation. In light of the current literature, international recommendations are supported that adequate diet‐derived n‐3 PUFAs might be beneficial in maintaining remission in IBD patients.
The respiratory epithelium constitutes the physical barrier between the human body and the environment, thus providing functional and immunological protection. It is often exposed to allergens, microbial substances, pathogens, pollutants, and environmental toxins, which lead to dysregulation of the epithelial barrier and result in the chronic inflammation seen in allergic diseases and asthma. This epithelial barrier dysfunction results from the disturbed tight junction formation, which are multi-protein subunits that promote cell-cell adhesion and barrier integrity. The increasing interest and evidence of the role of impaired epithelial barrier function in allergy and asthma highlight the need for innovative approaches that can provide new knowledge in this area. Here, we review and discuss the current role and mechanism of epithelial barrier dysfunction in developing allergic diseases and the effect of current allergy therapies on epithelial barrier restoration.
Background Lipid emulsions are a key component of total parenteral nutrition (TPN) and are administered to patients who are unable to ingest their daily required calories orally. Lipid emulsions rich with n–6 (ω-6) PUFAs are known to cause parenteral nutrition–associated liver disease and have inflammatory side effects, whereas n–3 PUFA-rich emulsions have favourable clinical outcomes. Objectives The present study used targeted lipid mediator analysis to investigate the metabolism of a n–3 PUFA-rich lipid emulsion and a n–6 PUFA-rich lipid emulsion in a mouse model of TPN and in primary human monocyte-derived macrophages (MDMs) and CD4+ T cells. Results Mice given n–3 PUFA-based TPN for 7 d had a less proinflammatory lipid mediator profile compared with those receiving n–6 PUFA-based TPN. This was characterized by higher concentrations of specialized pro-resolving mediators (SPMs) and endocannabinoids, including resolvin D (RvD) 1, maresin (MaR) 1, MaR2, protectin D1 (PD1), protectin DX (PDX), and the endocannabinoids eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) in the liver and RvD1, 17R-RvD1, RvD2, RvD3, RvD5, MaR1, MaR2, PD1, PDX, and EPEA and DHEA in the spleen. The spleen was identified as a source of high lipid mediator and SPM formation as lipid mediator concentrations were on average 25-fold higher than in the liver. Additionally, n–3 PUFA-treated primary human MDMs produced RvD5 and the endocannabinoids EPEA and DHEA, which was associated with an increased IL-10 secretion. In contrast, primary human CD4+ T cells showed only an increase in SPM precursors and an increase in the endocannabinoids EPEA and DHEA, which was associated with reduced cytokine expression. Conclusions This demonstrates that lipid mediators, particularly SPMs and endocannabinoids from spleen, could play a key role in facilitating the favorable clinical outcomes associated with the use of n–3 PUFA-rich lipid emulsions in TPN.
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