ReviewInflammation and immune regulation by 12/15-lipoxygenases
Section snippets
Lipoxygenases are lipid peroxidizing enzymes with multiple catalytic activities
LOXs catalyze the stereoselective oxygenation of polyunsaturated fatty acids containing at least one (1Z,4Z)-penta-1,4-dienoic system to the corresponding hydroperoxy derivatives [1]. LOX catalysis is a bimolecular reaction that requires the simultaneous presence of lipid substrate and atmospheric oxygen (Fig. 1). If one of the two substrates is limiting (e.g. severe hypoxia) the enzyme alters its catalytic activity and a different set of reaction products is formed (see below). Lipoxygenation
Tissue specific expression and expression regulation of 12/15-LOXs
In early years of eicosanoid research, conversion of exogenous arachidonic acid to 15-HETE was considered a proof for the presence of 12/15-LOX in a biological sample and in most cases the chirality of the reaction product was not investigated. Today we know that 15-HETE can be formed via alternative metabolic routes (non-enzymatic reactions, two human 15-LOXs, aspirin treated COX2) and thus, the classical activity assay is sufficient any more to prove 12/15-LOX expression. In state of the art
Regulation of immune cell function by 12/15-LOX expression
Induction of murine and human 12/15-LOX in monocytic cells by the TH2 cytokines, interleukins-4 (IL-4) and -13 (IL-13), and its suppression by interferon-γ (IFNγ) were early findings that hinted at a central role for this enzyme in immune regulation [48], [49], [88]. This has been extended by in vitro studies showing that peritoneal macrophages from mice lacking 12/15-LOX show a number of immune defects when compared with wild type. These include (i) decreased IL-4 induction of the scavenger
Pathophysiological role for 12/15-LOX in inflammatory vascular diseases
Inflammatory vascular disease encompasses a spectrum of disorders that includes atherosclerosis, diabetes and hypertension. A central involvement of the immune system in the pathophysiology of these diseases is well recognized. For example, leukocyte recruitment and activation as well as upregulation of both innate and acquired immunity, is a central feature. A role for 12/15-LOX in mediating pathogenic lipid peroxidation associated with inflammatory vascular disease has been discussed for many
What is the physiological role of 12/15-LOX in immune and inflammatory responses
12/15-LOXs are conserved in mammalian species indicating that they play an important physiological role. Without challenge, mice lacking 12/15-LOX appear normal without breeding problems or spontaneous pathophysiology. However, colonies are housed in microbiologically-regulated facilities and so will not be exposed to the same inflammatory and immune challenges experienced by free-living mammals. 12/15-LOX products interact with several inflammation-related signalling pathways often with
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