Activation and Regulation of Cellular Eicosanoid Biosynthesis

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States
The Scientific World Journal (Impact Factor: 1.73). 02/2007; 7:1273-84. DOI: 10.1100/tsw.2007.180
Source: PubMed


There is a growing appreciation for the wide variety of physiological responses that are regulated by lipid messengers. One particular group of lipid messengers, the eicosanoids, plays a central role in regulating immune and inflammatory responses in a receptor-mediated fashion. These mediators are related in that they are all derived from one polyunsaturated fatty acid, arachidonic acid. However, the various eicosanoids are synthesized by a wide variety of cell types by distinct enzymatic pathways, and have diverse roles in immunity and inflammation. In this review, the major pathways involved in the synthesis of eicosanoids, as well as key points of regulation, are presented.

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    • "COX-2 is also present at a basal level in certain tissues, but its expression is induced in inflammatory cells and tissues in response to cellular activation by endotoxin, cytokines, mitogens, and other stimulus [24, 25]. COX-2 is the main enzyme providing a mechanism for the generation of proinflammatory prostanoids, such as prostaglandin E2 (PGE2), a potent vasodilator, which enhances oedema formation [26, 27]. COX-3, in turn, has been cloned [28, 29], but its function have yet to be well studied. "
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    ABSTRACT: Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.
    01/2013; 2013(4):146716. DOI:10.1155/2013/146716
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    • "This inappropriate extension of neutrophil lifespan is accompanied by impaired clearance of apoptotic bodies and consequent inhibition of resolution of inflammation [23] [24]. Leukotriene B4 (LTB 4 ), a lipid mediator derived from arachidonic acid via 5-lipoxygenase pathway, is produced primarily by inflammatory cells, being considered a potent neutrophil activator [25] [26]. "
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    ABSTRACT: Leukotriene B(4), an arachidonic acid-derived lipid mediator, is a known proinflammatory agent that has a direct effect upon neutrophil physiology, inducing reactive oxygen species generation by the NADPH oxidase complex and impairing neutrophil spontaneous apoptosis, which in turn may corroborate to the onset of chronic inflammation. Despite those facts, a direct link between inhibition of neutrophil spontaneous apoptosis and NADPH oxidase activation by leukotriene B(4) has not been addressed so far. In this study, we aim to elucidate the putative role of NADPH oxidase-derived reactive oxygen species in leukotriene B(4)-induced anti-apoptotic effect. Our results indicate that NADPH oxidase-derived reactive oxygen species are critical to leukotriene B(4) pro-survival effect on neutrophils. This effect also relies on redox modulation of nuclear factor kappaB signaling pathway. We have also observed that LTB(4)-induced Bad degradation and mitochondrial stability require NADPH oxidase activity. All together, our results strongly suggest that LTB(4)-induced anti-apoptotic effect in neutrophils occurs in a reactive oxygen species-dependent manner. We do believe that a better knowledge of the molecular mechanisms underlying neutrophil spontaneous apoptosis may contribute to the development of more successful strategies to control chronic inflammatory conditions such as rheumatoid arthritis.
    Biochimica et Biophysica Acta 08/2012; 1823(10):1990-7. DOI:10.1016/j.bbamcr.2012.07.012 · 4.66 Impact Factor
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    • "COX-1 is associated with immediate biosynthesis of prostaglandins (several minutes after stimulation) which develop homeostatic functions; COX-2 is linked to delayed biosynthesis of prostaglandins (several hours after stimulus) which exert pathological effects. Other difference is the cellular localization; thus, COX-1 is expressed in endoplasmic reticulo, whereas COX-2 is situated in perinuclear membrane [7, 11]. "
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    ABSTRACT: Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. Several studies suggest that prostaglandins may play an important role in orchestrating interactions between different cells in several inflammatory diseases such as asthma. PGE(2) is important because of the multiplicity of its effects on immune response in respiratory diseases; however, respiratory system appears to be unique in that PGE(2) has beneficial effects. We described that the difference in airway function observed in patients with eosinophilic bronchitis and asthma could be due to differences in PGE(2) production. PGE(2) present in induced sputum supernatant from NAEB patients decreases BSMC proliferation, probably due to simultaneous stimulation of EP2 and EP4 receptors with inhibitory activity. This protective effect of PGE(2) may not only be the result of a direct action exerted on airway smooth-muscle proliferation but may also be attributable to the other anti-inflammatory actions.
    Mediators of Inflammation 03/2012; 2012(8651):645383. DOI:10.1155/2012/645383 · 3.24 Impact Factor
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