Protectin D1 (PD1) derived from docosahexaenoic acid (DHA) has shown promise in resolving inflammation. Mast cells are critical drivers of allergic inflammation, releasing inflammatory mediators such as histamine and pro-inflammatory cytokines. This study assesses the effectiveness of PD1 in counteracting mast cell-mediated allergic inflammation. In vivo, two well-established mouse models were employed: IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA). The oral administration of PD1 markedly suppressed PCA reactions, including ear swelling, plasma extravasation of Evans blue and mast cell degranulation. In the ASA model, oral PD1 administration dose-dependently alleviated hypothermia and reduced elevated serum levels of IgE, histamine, and IL-4. Mechanistic insights were gained through studies in the RBL-2H3 and primary mast cells derived from mouse bone marrow, where PD1 inhibited IgE-mediated degranulation and decreased intracellular calcium influx by blocking FcεRⅠ signaling pathways involving Lyn, Fyn, and Syk kinases. Additionally, PD1 suppressed pro-inflammatory cytokine production by inhibiting the activity of critical transcription factor; nuclear factor-κB. These findings suggest that PD1, a bioactive lipid derived from DHA, is a very promising therapeutic candidate for mast cell-derived allergic inflammation.

2017-02-01·Prostaglandins, leukotrienes, and essential fatty acids3区 · 医学

Identification and Profiling of Specialized Pro-Resolving Mediators in Human Tears by Lipid Mediator Metabolomics

3区 · 医学

Article

作者: Norris, Paul C ; Dartt, Darlene A ; Serhan, Charles N ; English, Justin T ; Hodges, Robin R

Specialized pro-resolving mediators (SPM), e.g. Resolvin D1, Protectin D1, Lipoxin A₄, and Resolvin E1 have each shown to be active in ocular models reducing inflammation. In general, SPMs have specific agonist functions that stimulate resolution of infection and inflammation in animal disease models. The presence and quantity of SPM in human emotional tears is of interest. Here, utilizing a targeted LC-MS-MS metabololipidomics based approach we document the identification of pro-inflammatory (Prostaglandins and Leukotriene B₄) and pro-resolving lipid mediators (D-series Resolvins, Protectin D1, and Lipoxin A₄) in human emotional tears from 12 healthy individuals. SPMs from the Maresin family (Maresin 1 and Maresin 2) were not present in these samples. Principal Component Analysis (PCA) revealed gender differences in the production of specific mediators within these tear samples as the SPMs were essentially absent in these female donors. These results indicate that specific SPM signatures are present in human emotional tears at concentrations known to be bioactive. Moreover, they will help to further appreciate the mechanisms of production and action of SPMs in the eye, as well as their physiologic roles in human ocular disease resolution.

2008-09-01·Intensive care medicine1区 · 医学

Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective

1区 · 医学

Review

作者: Joelle Singer ; Ronit Anbar ; Haim Shapiro ; Pierre Singer ; Jonathan Cohen ; Miryam Theilla

INTRODUCTION:

Fish oil-based nutrition is protective in severe critical care conditions. Regulation of the activity of transcription factor NF-kappaB is an important therapeutic effect of the major omega-3 fatty acids in fish oil, eicosapentaenoic and docosahexaenoic acid (EPA and DHA).

METHODS AND RESULTS:

Using the articles obtained by a Pubmed research, this article reviews three aspects of NF-kappaB/inflammatory inhibition by fish oil. (1) Inhibition of the NF-kappaB pathway at several subsequent steps: extracellular, free omega-3 inhibits the activation of the Toll-like receptor 4 by endotoxin and free saturated fatty acids. In addition, EPA/DHA blocks the signaling cascade between Toll-like/cytokine receptors and the activator of NF-kappaB, IKK. Oxidized omega-3 also interferes with the initiation of transcription by NF-kappaB. (2) The altered profile of lipid mediators generated during inflammation, with production of the newly identified, DHA-derived inflammation-resolving mediator classes (in addition to the formation of less pro-inflammatory eicosanoids from EPA). Resolvin D1 and Protectin D1 are potent, endogenous, DHA-derived lipid mediators that attenuate neutrophil migration and tissue injury in peritonitis and ischemia-reperfusion injury. Their production is increased in the later stages of an inflammatory response, at which time they enhance the removal of neutrophils. (3) Modulation of vagal tone with potential anti-inflammatory effects: vagal fibers innervating the viscera down-regulate inflammation by activating nicotinic receptors upon infiltrating and resident macrophages. Stimulation of the efferent vagus is therapeutic in experimental septic shock. Fish oil supplementation increases vagal tone following myocardial infarction and in experimental human endotoxinemia.

CONCLUSION:

It remains to be shown whether these pleiotropic actions of EPA/DHA contribute to fish oil's therapeutic effect in sepsis.

100 项与 Protectin D1 相关的药物交易

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