hydroxyeicosatetraenoic acids

Summary

Summary: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.

Top Publications

  1. Sodhi K, Wu C, Cheng J, Gotlinger K, Inoue K, Goli M, et al. CYP4A2-induced hypertension is 20-hydroxyeicosatetraenoic acid- and angiotensin II-dependent. Hypertension. 2010;56:871-8 pubmed publisher
  2. Singh H, Schwartzman M. Renal vascular cytochrome P450-derived eicosanoids in androgen-induced hypertension. Pharmacol Rep. 2008;60:29-37 pubmed
  3. Eid A, Gorin Y, Fagg B, Maalouf R, Barnes J, Block K, et al. Mechanisms of podocyte injury in diabetes: role of cytochrome P450 and NADPH oxidases. Diabetes. 2009;58:1201-11 pubmed publisher
    ..Inhibition of selected cytochrome P450 isoforms prevented podocyte apoptosis and reduced proteinuria in diabetes. ..
  4. Ishizuka T, Cheng J, Singh H, Vitto M, Manthati V, Falck J, et al. 20-Hydroxyeicosatetraenoic acid stimulates nuclear factor-kappaB activation and the production of inflammatory cytokines in human endothelial cells. J Pharmacol Exp Ther. 2008;324:103-10 pubmed
    ..It seems that 20-HETE triggers NF-kappaB and MAPK/ERK activation and that both signaling pathways participate in the cellular mechanisms by which 20-HETE activates vascular endothelial cells. ..
  5. Minuz P, Jiang H, Fava C, Turolo L, Tacconelli S, Ricci M, et al. Altered release of cytochrome p450 metabolites of arachidonic acid in renovascular disease. Hypertension. 2008;51:1379-85 pubmed publisher
    ..Altered cytochrome P450 arachidonic acid metabolism may contribute to the vascular and tubular abnormalities of renovascular disease. ..
  6. Fleming I. Vascular cytochrome p450 enzymes: physiology and pathophysiology. Trends Cardiovasc Med. 2008;18:20-5 pubmed publisher
    ..Epoxyeicosatrienoic acids are recognized as lipid mediators that participate in vascular signaling processes such as the acute regulation of vascular tone and the processes of inflammation and angiogenesis. ..
  7. Bajpai A, Blaskova E, Pakala S, Zhao T, Glasgow W, Penn J, et al. 15(S)-HETE production in human retinal microvascular endothelial cells by hypoxia: Novel role for MEK1 in 15(S)-HETE induced angiogenesis. Invest Ophthalmol Vis Sci. 2007;48:4930-8 pubmed
    ..In addition, 15(S)-HETE, through MEK1-dependent activation of ERK1/2 and JNK1, stimulates the angiogenic differentiation of HRMVECs and basement membrane matrix plug angiogenesis. ..
  8. Imig J. Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function. Prostaglandins Other Lipid Mediat. 2013;104-105:2-7 pubmed publisher
    ..These findings have demonstrated the important contributions that 20-HETE and EETs play in the regulation of renal microvascular function. ..
  9. Nieves D, Moreno J. Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth. J Lipid Res. 2006;47:2681-9 pubmed
    ..Our results show that 3T6 fibroblasts synthesized hydroxyeicosatetraenoic acids (HETEs) such as 12-HETE through the cytochrome P-450 (CYP450) pathway...

More Information

Publications62

  1. Jacobs E, Zhu D, Gruenloh S, Lopez B, Medhora M. VEGF-induced relaxation of pulmonary arteries is mediated by endothelial cytochrome P-450 hydroxylase. Am J Physiol Lung Cell Mol Physiol. 2006;291:L369-77 pubmed
    ..Given the unique expression of 20-HETE-forming CYP4 in BPAECs vs. systemic arterial endothelial cells, CYP4 may be an important mediator of endothelial-dependent vasoreactivity in PAs. ..
  2. Williams J, Sharma M, Anjaiahh S, Falck J, Roman R. Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier. Am J Physiol Renal Physiol. 2007;293:F501-5 pubmed
    ..These results indicate that glomeruli produce 20-HETE, EETs, diHETEs, and HETEs and that endogenously formed 20-HETE and EETs play an essential role in the maintenance of the glomerular permeability barrier to albumin. ..
  3. Michaelis U, Fisslthaler B, Barbosa Sicard E, Falck J, Fleming I, Busse R. Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis. J Cell Sci. 2005;118:5489-98 pubmed
    ..Taken together, these data indicate that CYP 2C-derived EETs significantly affect the sequence of angiogenic events under hypoxic conditions. ..
  4. Cheng J, Wu C, Gotlinger K, Zhang F, Falck J, Narsimhaswamy D, et al. 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling. J Pharmacol Exp Ther. 2010;332:57-65 pubmed publisher
    ..The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation. ..
  5. Park F, Sweeney W, Jia G, Akbulut T, Mueller B, Falck J, et al. Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD. Am J Physiol Renal Physiol. 2009;296:F575-82 pubmed publisher
    ..These studies indicate a potential role of 20-HETE in cyst formation in the orthologous rodent PCK model of ARPKD. ..
  6. Yin H, Davis T, Porter N. Simultaneous analysis of multiple lipid oxidation products in vivo by liquid chromatographic-mass spectrometry (LC-MS). Methods Mol Biol. 2010;610:375-86 pubmed publisher
    ..This LC-MS technique can be applied to study the free radical oxidation mechanism in vitro and assess the oxidative stress status in biological tissues and fluids. ..
  7. Stec D, Gannon K, Beaird J, Drummond H. 20-Hydroxyeicosatetraenoic acid (20-HETE) stimulates migration of vascular smooth muscle cells. Cell Physiol Biochem. 2007;19:121-8 pubmed
    ..Blockade of MEK and PI3K all abolished the increase in 20-HETE mediated migration. 20-HETE stimulates PDGF-mediated VSM migration acting through pathways that involve MEK and PI3K. ..
  8. Ward N, Hodgson J, Puddey I, Beilin L, Croft K. 20-Hydroxyeicosatetraenoic acid is not associated with circulating insulin in lean to overweight humans. Diabetes Res Clin Pract. 2006;74:197-200 pubmed
    ..The results of the present study suggest that the observed positive association between urinary 20-HETE excretion and BMI may not be related to circulating insulin levels or insulin resistance. ..
  9. Lee S, Rangiah K, Williams M, Wehr A, DuBois R, Blair I. Cyclooxygenase-2-mediated metabolism of arachidonic acid to 15-oxo-eicosatetraenoic acid by rat intestinal epithelial cells. Chem Res Toxicol. 2007;20:1665-75 pubmed
    ..These data further highlight the importance of endogenous COX-2-mediated lipid peroxidation and illustrate the necessity to monitor eicosanoid formation from endogenous stores of AA in cell culture experiments. ..
  10. Wu C, Schwartzman M. The role of 20-HETE in androgen-mediated hypertension. Prostaglandins Other Lipid Mediat. 2011;96:45-53 pubmed publisher
    ..In this review, we will discuss the pro-hypertensive effects of 20-HETE and its role in androgen-induced vascular dysfunction and hypertension. ..
  11. Wittwer J, Hersberger M. The two faces of the 15-lipoxygenase in atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2007;77:67-77 pubmed
    ..This will now allow large studies to investigate an association of 15-LOX with coronary artery disease and to answer the question whether 15-LOX is pro- or anti-atherogenic in humans. ..
  12. Guo A, Arbab A, Falck J, Chen P, Edwards P, Roman R, et al. Activation of vascular endothelial growth factor through reactive oxygen species mediates 20-hydroxyeicosatetraenoic acid-induced endothelial cell proliferation. J Pharmacol Exp Ther. 2007;321:18-27 pubmed
    ..Thus, 20-HETE may be involved in the regulation of EC functions, such as angiogenesis. ..
  13. Muller D, Schmidt C, Barbosa Sicard E, Wellner M, Gross V, Hercule H, et al. Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation. Biochem J. 2007;403:109-18 pubmed
    ..Cyp4a12a expression determines the sex- and strain-specific differences in 20-HETE generation and may explain sex and strain differences in the susceptibility to hypertension and target organ damage. ..
  14. Miyata N, Roman R. Role of 20-hydroxyeicosatetraenoic acid (20-HETE) in vascular system. J Smooth Muscle Res. 2005;41:175-93 pubmed
    Cytochrome P450s (P450) metabolize arachidonic acid (AA) to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs)...
  15. Cheng J, Ou J, Singh H, Falck J, Narsimhaswamy D, Pritchard K, et al. 20-hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling. Am J Physiol Heart Circ Physiol. 2008;294:H1018-26 pubmed
  16. Al Shabrawey M, Mussell R, Kahook K, Tawfik A, Eladl M, Sarthy V, et al. Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: implications in retinal neovascularization. Diabetes. 2011;60:614-24 pubmed publisher
    ..The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV)...
  17. Williams J, Murphy S, Burke M, Roman R. 20-hydroxyeicosatetraeonic acid: a new target for the treatment of hypertension. J Cardiovasc Pharmacol. 2010;56:336-44 pubmed publisher
    ..This review summarizes the rationale for the development of drugs that target the 20-HETE pathway for the treatment of hypertension and associated cardiovascular complications. ..
  18. Morin C, Sirois M, Echave V, Gomes M, Rousseau E. Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1037-44 pubmed
    ..Together, these results indicate that 20-HETE-dependent activation of BK(Ca) channels is responsible for the hyperpolarization and controlled relaxation of ASM in human distal bronchi. ..
  19. Yue H, Jansen S, Strauss K, Borenstein M, Barbe M, Rossi L, et al. A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in r. J Pharm Biomed Anal. 2007;43:1122-34 pubmed
    ..and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2alpha), PGE(2), PGD(2), PGJ(2), 14,15-..
  20. Dioszeghy V, Rosas M, Maskrey B, Colmont C, Topley N, Chaitidis P, et al. 12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo. J Immunol. 2008;181:6514-24 pubmed
    ..No changes in neutrophil or lymphocyte numbers were seen. In summary, endogenous 12/15-LOX defines the resident MPhi population and regulates both the recruitment of monocytes/Mphi and cytokine response to bacterial products in vivo. ..
  21. Dhanasekaran A, Bodiga S, Gruenloh S, Gao Y, Dunn L, Falck J, et al. 20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells. Am J Physiol Heart Circ Physiol. 2009;296:H777-86 pubmed publisher
    ..In summary, 20-HETE may afford a survival advantage to BPAECs through activation of prosurvival PI3-kinase and Akt pathways, NADPH oxidase activation, and NADPH oxidase-derived superoxide. ..
  22. Fang X, Dillon J, Hu S, Harmon S, Yao J, Anjaiah S, et al. 20-carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors alpha and gamma. Prostaglandins Other Lipid Mediat. 2007;82:175-84 pubmed
    ..87+/-0.12 microM) and PPARgamma (Kd=1.7+/-0.5 microM). These findings suggest that 20-COOH-AA, a relatively stable metabolite of 20-HETE, might function as an endogenous dual activator of PPARalpha and PPARgamma. ..
  23. Kim D, Vanella L, Inoue K, Burgess A, Gotlinger K, Manthati V, et al. Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ. Stem Cells Dev. 2010;19:1863-73 pubmed publisher
    ..These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome. ..
  24. Dolegowska B, Blogowski W, Safranow K, Domanski L, Jakubowska K, Olszewska M. Lipoxygenase-derived hydroxyeicosatetraenoic acids--novel perioperative markers of early post-transplant allograft function?. Nephrol Dial Transplant. 2010;25:4061-7 pubmed publisher
    ..91 and P = 0.31, respectively). We hereby report that human kidney transplantations are accompanied by significant changes in LOX AA metabolism, which strongly influences and predicts early (1 year) post-transplant graft function. ..
  25. Yu M, Lopez B, Dos Santos E, Falck J, Roman R. Effects of 20-HETE on Na+ transport and Na+ -K+ -ATPase activity in the thick ascending loop of Henle. Am J Physiol Regul Integr Comp Physiol. 2007;292:R2400-5 pubmed
    ..These findings indicate that 20-HETE secondarily inhibits Na+ transport in the mTALH of the rat, at least, in part by inhibiting the Na+ -K+ -ATPase activity and raising [Na+]i. ..
  26. Nilakantan V, Maenpaa C, Jia G, Roman R, Park F. 20-HETE-mediated cytotoxicity and apoptosis in ischemic kidney epithelial cells. Am J Physiol Renal Physiol. 2008;294:F562-70 pubmed publisher
  27. Moreno J. New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development. Biochem Pharmacol. 2009;77:1-10 pubmed publisher
    ..the conversion of arachidonic acid (AA) to hydroperoxyeicosatetraenoic acids that are then reduced to hydroxyeicosatetraenoic acids (HETE) by glutathione peroxidase...
  28. Inoue R, Jensen L, Jian Z, Shi J, Hai L, Lurie A, et al. Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/omega-hydroxylase/20-HETE pathways. Circ Res. 2009;104:1399-409 pubmed publisher
  29. Tsai I, Croft K, Puddey I, Beilin L, Barden A. 20-Hydroxyeicosatetraenoic acid synthesis is increased in human neutrophils and platelets by angiotensin II and endothelin-1. Am J Physiol Heart Circ Physiol. 2011;300:H1194-200 pubmed publisher
  30. Guo A, Sheng J, Scicli G, Arbab A, Lehman N, Edwards P, et al. Expression of CYP4A1 in U251 human glioma cell induces hyperproliferative phenotype in vitro and rapidly growing tumors in vivo. J Pharmacol Exp Ther. 2008;327:10-9 pubmed publisher
    ..This suggests that 20-HETE may have proto-oncogenic properties in U251 human gliomas. Further studies are needed to determine whether 20-HETE plays a role promoting growth of some human gliomas. ..
  31. Wang Z, Tang X, Li Y, Leu C, Guo L, Zheng X, et al. 20-Hydroxyeicosatetraenoic acid inhibits the apoptotic responses in pulmonary artery smooth muscle cells. Eur J Pharmacol. 2008;588:9-17 pubmed publisher
    ..Such effects were reversed in the presence of 17-ODYA. Thus, these findings indicate that 20-HETE protects PASMCs against apoptosis by acting on, at least in part, the intrinsic apoptotic pathway. ..
  32. Wang J, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, et al. Endothelial dysfunction and hypertension in rats transduced with CYP4A2 adenovirus. Circ Res. 2006;98:962-9 pubmed
  33. Maskrey B, Bermudez Fajardo A, Morgan A, Stewart Jones E, Dioszeghy V, Taylor G, et al. Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase. J Biol Chem. 2007;282:20151-63 pubmed
    ..2), did not reveal PE esters, indicating that this modification is restricted to the LOX pathway. In summary, we show formation of PE-esterified HETEs in immune cells that may contribute to LOX signaling in inflammation. ..
  34. Kowal Bielecka O, Kowal K, Distler O, Rojewska J, Bodzenta Lukaszyk A, Michel B, et al. Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators. Arthritis Rheum. 2005;52:3783-91 pubmed
    ..Targeting the 5-LOX/15-LOX balance may be of practical value in the treatment of SLD. ..
  35. Altmann R, Hausmann M, Spottl T, Gruber M, Bull A, Menzel K, et al. 13-Oxo-ODE is an endogenous ligand for PPARgamma in human colonic epithelial cells. Biochem Pharmacol. 2007;74:612-22 pubmed
    ..High amounts of 13-Oxo-ODE can be induced in CECs by stimulation of linoleic acid metabolism. 13-Oxo-ODE binds to PPARgamma and has anti-inflammatory effects. 13-HODE dehydrogenase might be a therapeutic target in IBD. ..
  36. Wen Y, Gu J, Vandenhoff G, Liu X, Nadler J. Role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages. Am J Physiol Heart Circ Physiol. 2008;294:H1933-8 pubmed publisher
    ..These results suggest a potentially important mechanism linking 12/15-LO activation to MCP-1 expression that induces inflammatory cell infiltration. ..
  37. Ito O, Nakamura Y, Tan L, Ishizuka T, Sasaki Y, Minami N, et al. Expression of cytochrome P-450 4 enzymes in the kidney and liver: regulation by PPAR and species-difference between rat and human. Mol Cell Biochem. 2006;284:141-8 pubmed
  38. Dunn K, Renic M, Flasch A, Harder D, Falck J, Roman R. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295:H2455-65 pubmed publisher
    ..These results indicate the production of 20-HETE is elevated in the cerebral vasculature of SHRSP and contributes to oxidative stress, endothelial dysfunction, and the enhanced sensitivity to ischemic stroke in this hypertensive model. ..
  39. Tsai I, Croft K, Mori T, Falck J, Beilin L, Puddey I, et al. 20-HETE and F2-isoprostanes in the metabolic syndrome: the effect of weight reduction. Free Radic Biol Med. 2009;46:263-70 pubmed publisher
    ..20-HETE and oxidative stress may be important mediators of cardiovascular disease risk in the MetS. Although a 4% reduction in body weight reduced BP, there were no changes in plasma or urinary 20-HETE or F(2)-isoprostanes. ..
  40. Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A, et al. Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension. Hypertension. 2007;50:123-9 pubmed
    ..05). The results strongly implicate vascular cytochrome P450 4A-derived 20-hydroxyeicosatetraenoic acid in the development of androgen-induced endothelial dysfunction and hypertension. ..
  41. Alexanian A, Rufanova V, Miller B, Flasch A, Roman R, Sorokin A. Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma cell proliferation and tumor growth. Anticancer Res. 2009;29:3819-24 pubmed
    ..c.) administered daily to athymic nude mice implanted subcutaneously with 786-O cells reduced the growth of the tumors by 84 % compared to vehicle (p<0.001). 20-HETE is required for proliferation of human renal epithelial cancer. ..
  42. Goh J, Baird A, O Keane C, Watson R, Cottell D, Bernasconi G, et al. Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo. J Immunol. 2001;167:2772-80 pubmed
    ..Our observations further expand the anti-inflammatory profile of these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for the treatment of inflammatory bowel disease. ..
  43. Ward N, Rivera J, Hodgson J, Puddey I, Beilin L, Falck J, et al. Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans. Circulation. 2004;110:438-43 pubmed
    ..Given the negative modulatory role of nitric oxide on omega-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology. ..
  44. Chuang S, Helvig C, Taimi M, Ramshaw H, Collop A, Amad M, et al. CYP2U1, a novel human thymus- and brain-specific cytochrome P450, catalyzes omega- and (omega-1)-hydroxylation of fatty acids. J Biol Chem. 2004;279:6305-14 pubmed
    ..Based on the ability of CYP2U1 to generate bioactive eicosanoid derivatives, we postulate that CYP2U1 plays an important physiological role in fatty acid signaling processes in both cerebellum and thymus. ..
  45. Laffer C, Laniado Schwartzman M, Nasjletti A, Elijovich F. 20-HETE and circulating insulin in essential hypertension with obesity. Hypertension. 2004;43:388-92 pubmed
    ..Findings in experimental models suggest that an inhibitory effect of insulin on cytochrome P4504A, rather than effects of insulin on membrane-bound arachidonic acid or on its release to the cytosol, may explain our observation. ..
  46. Natarajan R, Nadler J. Lipid inflammatory mediators in diabetic vascular disease. Arterioscler Thromb Vasc Biol. 2004;24:1542-8 pubmed
    ..This review evaluates these inflammatory and proatherogenic pathways in the pathogenesis of diabetic vascular disease. ..
  47. Ljubimov A, Grant M. P450 in the angiogenesis affair: the unusual suspect. Am J Pathol. 2005;166:341-4 pubmed
  48. Ariel A, Chiang N, Arita M, Petasis N, Serhan C. Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J Immunol. 2003;170:6266-72 pubmed
    ..Moreover, they provide potential counterregulatory signals in communication(s) between the innate and acquired immune systems. ..
  49. Yao Y, Clark C, Trojanowski J, Lee V, Pratico D. Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment. Ann Neurol. 2005;58:623-6 pubmed
    ..These results suggest that the activation of this enzyme occurs early in the course of AD, before the onset of overt dementia, thereby implicating 12/15LOX-mediated lipid peroxidation in the pathogenesis of AD. ..
  50. Profita M, Sala A, Siena L, Henson P, Murphy R, Paterno A, et al. Leukotriene B4 production in human mononuclear phagocytes is modulated by interleukin-4-induced 15-lipoxygenase. J Pharmacol Exp Ther. 2002;300:868-75 pubmed
    ..Whereas this effect did not reflect changes in 5-LO and FLAP mRNA expression, synthetic 15(S)-HETE was able to significantly inhibit the synthesis of LTB4, without affecting AA release. ..
  51. Zhang F, Deng H, Kemp R, Singh H, Gopal V, Falck J, et al. Decreased levels of cytochrome P450 2E1-derived eicosanoids sensitize renal arteries to constrictor agonists in spontaneously hypertensive rats. Hypertension. 2005;45:103-8 pubmed
  52. Holla V, Adas F, Imig J, Zhao X, Price E, Olsen N, et al. Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension. Proc Natl Acad Sci U S A. 2001;98:5211-6 pubmed
  53. Shankaranarayanan P, Nigam S. IL-4 induces apoptosis in A549 lung adenocarcinoma cells: evidence for the pivotal role of 15-hydroxyeicosatetraenoic acid binding to activated peroxisome proliferator-activated receptor gamma transcription factor. J Immunol. 2003;170:887-94 pubmed
    ..In conclusion, IL-4-induced apoptosis may contribute to severe loss of alveolar structures and infiltration of eosinophils, mononuclear phagocytes, etc., into the lung tissue of chronic asthma patients. ..