lipoxins การใช้

• Other SPMs include the lipoxins, protectin D1 and its related products, and the maresins.
• The lipoxins and epi-lipoxins are potent anti-inflammatory agents and may contribute to the overall activities of the two COX's as well as to aspirin.
• The lipoxins and epi-lipoxins are potent anti-inflammatory agents and may contribute to the overall activities of the two COX's as well as to aspirin.
• There are multiple subfamilies of eicosanoids, including most prominently the prostaglandins, thromboxanes, leukotrienes, lipoxins, resolvins, and eoxins but also others as noted in the following Nomenclature section.
• Furthermore, aspirin-treated COX-2 metabolizes arachidonic acid almost exclusively to 15 ( " R " )-HETE which product can be further metabolized to epi-lipoxins.
• In another pathway, ALOX5 may act in series with a second lipoxygenase enzyme, ALOX15, to metabolize AA to lipoxin A4 ( LxA4 ) and LxB4 ( see Specialized pro-resolving mediators # Lipoxins ).
• However, the most studied and accepted role for FPR2 receptors is in mediating the actions of the cited lipoxins and resolvins in dampening and resolving a wide range of inflammatory reactions ( see lipoxin, Epi-lipoxin, and resolvin ).
• Both receptor types bind and are activated by a series of formylated oligopeptide chemotactic factors but FLP2 receptor appears to be a promiscuous receptor in that it also binds to and is activated by lipoxins and resolvins as well as various polypeptides and proteins.
• By metabolizing ?-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into lipoxins and resolvins, 15-LOX-1 is thought to be one mechanism by which dietary ?-3 polyunsaturated fatty acids, particularly fish oil, may act to reduce the incidence and / or progression of certain cancers.
• However, lipoxins also have harmful effects in these models : aerosol infection with " Mycobacterium tuberculosis " in transgenic mice defective in ALOX5, which contributes to LX synthesis, exhibited far less sever inflammation and better survival than control mice; and treatment of the transgenic mice with oral LXA 4 reversed the protective effect of ALOX5 deletion.
• For example, ALOX5 acts with ALOX12 or aspirin-treated COX-2 to metabolize arachidonic acid to lipoxins and with cytochrome P450 monooxygenase ( s ), bacterial cytochrome P450 ( in infected tissues ), or aspirin-treated COX2 to metabolize eicosapentaenoic acid to the E series resolvins ( RvEs ) ( see Specialized pro-resolving mediators ).
• Similar to various other AA metabolites such as LTA4 and 5-oxo-eicosatetraenoic acid, cells and tissues may convert LXs to 20-hydroxy products by omega oxidation; they also have been shown to ligate LXA 4 to glutathione to form cysteinyl-lipoxins, initially LXC 4, which is then sequentially metabolized to LXD 4 and LXE 4.
• They form later than the ALOX5-derived chemotactic factors in the inflammatory response and are thought to limit or resolve these responses by, for example, inhibiting the entry of circulating leukocytes into inflamed tissues, inhibiting the pro-inflammatory action of the leukocytes, promoting leukocytes to exit from inflammatory sites, and stimulating leukocyte apoptosis ( see specialized pro-resolving mediators and lipoxins ).
• The 7 mouse FPR receptors have e " 50 % amino acid sequence identity with each other as well as with the three human FPR receptors . " Fpr2 " and " mFpr-rs1 " bind with high affinity and respond to lipoxins but have little or no affinity for, and responsiveness to, formyl peptides; they thereby share key properties with human FPR2;
• Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the prostaglandins, converts this enzyme's activity from a prostaglandin-forming cyclooxygenase to a lipoxygenase-like enzyme : aspirin-treated COX-2 metabolizes a variety of polyunsaturated fatty acids to hydroperoxy products which are then further metabolized to specialized proresolving mediators such as the aspirin-triggered lipoxins, aspirin-triggered resolvins, and aspirin-triggered maresins.
• Specialized pro-resolving mediators are cell-derived metabolites of certain polyunsaturated fatty acids viz . : arachidonic acid which is metabolized to the lipoxins; eicosapentaenoic acid which is metabolized to the Resolvin E's; docosahexaenoic acid which is metablized to the Resolvin D's, Maresins, and Neuroprotectins; and n-3 docosapentaenoic acid which is metabolized to the n-3 docosapentaenoic acid-derived resolvins and n-3 docosapentaenoic acid-derived neuroprotectins ( See Specialized pro-resolving mediators ).
• For example, ALOX5 and ALOX15 or, alternatively, ALOX5 and ALOX12 can act serially to metabolize arachidonic acid into lipoxins ( see 15-hydroxyicosatetraenoic acid # Further metabolism of 15 ( S )-HpETE, 15 ( S )-HETE, 15 ( R )-HpETE, 15 ( R )-HETE, and 15-oxo-ETE and lipoxin # Biosynthesis ) while ALOX15 and possibly ALOX15B can act with ALOX5 to metabolize eicosapentaenoic acid to resolvin D's ( see resolvin # Production ).
• Studies find that : a ) mouse Fpr1 is an ortholog of human FPR1, responding to many bacterial-and mitochondrial-derived formyl peptides but only minimally to FMLP and having certain pharmacologic properties in common with human FPR2 / ALX; b ) mouse Fpr2 and mFpr-rs1 bind with high affinity and respond to lipoxins but have little affinity for or responsiveness to formyl peptides and therefore share key properties with human FPR2 / ALX; and c ) based on its predominantly intracellular distribution, mFpr-rs1 correlates, and therefore may share functionally, with human FPR3;
• While metabolizing arachidonic acid primarily to PGG2, COX-2 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids ( i . e ., 15-HETEs ) composed of ~ 22 % 15 ( " R " )-HETE and ~ 78 % 15 ( " S " )-HETE stereoisomers as well as a small amount of 11 ( " R " )-HETE . The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of agents, the lipoxins.
• While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids ( i . e ., 15-HETEs ) composed of ~ 22 % 15 ( " R " )-HETE and ~ 78 % 15 ( " S " )-HETE stereoisomers as well as a small amount of 11 ( " R " )-HETE . The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of anti-inflammatory agents, the lipoxins.