The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering

Ariel, Amiram; Li, Pin‐Lan; Wang, Wei; Tang, Wang-Xian; Fredman, Gabrielle; Hong, Song; Gotlinger, Katherine; Serhan, Charles N.

doi:10.1074/jbc.m509796200

Cited by 219 publications

(205 citation statements)

References 49 publications

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“…These lipid mediators have been shown to decrease formation of inflammatory cytokines such as TNF␣, IL-6, and others (31,32). Our data confirm decreased levels of cytokines, which may be due to the documented lower NF-B activity in fat-1 mice shown here.…”

Section: Discussionsupporting

confidence: 80%

Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis

Hudert

Weylandt

Lü

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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360

278

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Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are the precursors of potent lipid mediators and play an important role in regulation of inflammation. Generally, n-6 PUFA promote inflammation whereas n-3 PUFA have antiinflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived proinflammatory eicosanoids. Newly discovered resolvins and protectins are potent antiinflammatory lipid mediators derived directly from n-3 PUFA with distinct pathways of action. However, the role of the n-3 PUFA tissue status in the formation of these antiinflammatory mediators has not been addressed. Here we show that an increased n-3 PUFA tissue status in transgenic mice that endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant formation of antiinflammatory resolvins and effective reduction in inflammation and tissue injury in colitis. The endogenous increase in n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid mediators such as leukotriene B4 and prostaglandin E2. The observed inflammation protection might result from decreased NF-B activity and expression of TNF␣, inducible NO synthase, and IL-1␤, with enhanced mucoprotection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the fat-1 transgenic mouse as a new experimental model for the study of n-3 PUFA-derived lipid mediators. They add insight into the molecular mechanisms of inflammation protection afforded by n-3 PUFA through formation of resolvins and protectins other than inhibition of n-6 PUFA-derived eicosanoid formation.inflammation ͉ inflammatory bowel disease ͉ lipid mediators ͉ resolvins ͉ protectins

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Section: Discussionsupporting

confidence: 80%

Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis

Hudert

Weylandt

Lü

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

360

278

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“…However, they appear to exert their effects through a different set of receptors (75). Several studies have shown that certain members of the resolvin family suppress neutrophil infiltration and cytokine secretion in animal models of inflammation (42,76). Also, they have been shown to be protective following brain injury after experimental stroke (77), for insulin-resistance and hepatic steatosis in obesity (78), airway inflammation (79, 80), and they enhanced wound healing and suppressed colitis (75) in mouse models of inflammatory diseases.…”

Section: Anti-inflammatory Effects Of Lipoxins and Resolvinsmentioning

confidence: 99%

“…One of the pathways for the D-series involves 5-and 15-lipoxygenase activity (42), with evidence that 15-lipoxygenase activity from leukocytes or epithelial cells leads to 17S-hydroxy-DHA (42,43). This has anti-inflammatory effects and can be metabolized further by leukocyte 5-lipoxygenase to the D-series of resolvins or by an epoxydase to the protectins (40,42,44).…”

Section: Biosynthesis Of Resolvins and Protectinsmentioning

confidence: 99%

“…This has anti-inflammatory effects and can be metabolized further by leukocyte 5-lipoxygenase to the D-series of resolvins or by an epoxydase to the protectins (40,42,44). In the second pathway, the intermediate metabolite 17R-hydroxy-DHA is formed from DHA by acetylated COX-2 (40) and further metabolized into the D-series of resolvins and protectins (45).…”

Section: Biosynthesis Of Resolvins and Protectinsmentioning

confidence: 99%

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Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins

Hersberger

2010

Clinical Chemistry and Laboratory Medicine

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Atherogenesis is an inflammatory process with leukocytes infiltrating the arterial intima. The lipoxygenase pathways play a role in leukocyte recruitment through the generation of two classes of arachidonic acid lipid mediators, the leukotrienes and the lipoxins, and one class of omega-3 fatty acid metabolites, the resolvins. There is evidence from animal studies and human genetic studies that the leukotrienes and the enzymes necessary for their generation play a role in atherosclerosis, and possibly even in the development of the vulnerable plaque. Less is known about the effect of the anti-inflammatory lipid mediators in atherosclerosis, the lipoxins and the resolvins. Studies modulating the activity of an enzyme necessary for the production of these lipid mediators, 12/15-lipoxygenase, showed discrepant results in several animal models. Also, human genetic studies have not clearly dissected the effect of the enzyme on atherosclerosis. However, stable forms of the lipoxins and the resolvins protect animals from inflammatory diseases. Whether blocking the leukotrienes or applying anti-inflammatory lipoxins and resolvins will be effective in attenuating human atherosclerosis needs to be demonstrated in future studies. In this review, the biosynthesis of these lipid mediators, their biological effects and the evidence for their possible role in atherosclerosis are discussed with an emphasis on human disease.

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“…Since then, additional pro-inflammatory products have been discovered (Feltenmark et al, 2008). On the other hand, anti-inflammatory and/or pro-resolving lipids generated by mammalian isoforms have also been identified, including lipoxins (Serhan et al, 1984;Maderna & Gordon, 2009), resolvins (Serhan et al, 2004), protectins (Ariel et al, 2005;Schwab et al, 2007) and maresins (Serhan et al, 2009). Therefore, LOX products play important roles in the development of acute inflammation but they have also been implicated in inflammatory resolution.…”

mentioning

confidence: 99%

Lipoxygenase-Quercetin Interaction: A Kinetic Study Through Biochemical and Spectroscopy Approaches

Chedea¹,

Vicaş²,

Socaciu³

et al. 2012

Biochemical Testing

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The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering

Cited by 219 publications

References 49 publications

Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis

Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis

Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins

Lipoxygenase-Quercetin Interaction: A Kinetic Study Through Biochemical and Spectroscopy Approaches

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