Lipoxygenase products regulate nitric oxide and inducible nitric oxide synthase production in interleukin-1beta stimulated vascular smooth muscle cells.

In cultured vascular smooth muscle cells (VSMCs), interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1beta also activates phospholipase A2 (PLA2), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1beta-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA2 (sPLA2) inhibitor, at 1 to 10 micromol/l reduced IL-1beta-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10 micromol/l), the LOX inhibitor, also reduced IL-1beta (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(S)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1beta-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs.

[1]  J. Astern,et al.  Genetic Deficiency of Inducible Nitric Oxide Synthase Reduces Atherosclerosis and Lowers Plasma Lipid Peroxides in Apolipoprotein E–Knockout Mice , 2001, Circulation.

[2]  Ling-Ling Yang,et al.  Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. , 2001, Biochemical pharmacology.

[3]  J. Rossi,et al.  Ribozyme-Mediated Inhibition of Rat Leukocyte-Type 12-Lipoxygenase Prevents Intimal Hyperplasia in Balloon-Injured Rat Carotid Arteries , 2001, Circulation.

[4]  M. Shichiri,et al.  Cytokine-activated p42/p44 MAP kinase is involved in inducible nitric oxide synthase gene expression independent from NF-kappaB activation in vascular smooth muscle cells. , 2000, Hypertension research : official journal of the Japanese Society of Hypertension.

[5]  A. Takeshita,et al.  Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a rat model of chronic inhibition of nitric oxide synthesis by its cholesterol-lowering independent actions. , 2000, Hypertension research : official journal of the Japanese Society of Hypertension.

[6]  U. Ikeda,et al.  Effects of aspirin-like drugs on nitric oxide synthesis in rat vascular smooth muscle cells. , 2000, Hypertension.

[7]  U. Ikeda,et al.  Direct effects of statins on cells primarily involved in atherosclerosis. , 2000, Hypertension research : official journal of the Japanese Society of Hypertension.

[8]  H. Yagi,et al.  Lipoxygenase inhibition decreases neointimal formation following vascular injury. , 1999, Atherosclerosis.

[9]  R. Ross.  Atherosclerosis is an inflammatory disease , 1999 .

[10]  D. Rader,et al.  Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. , 1999, The Journal of clinical investigation.

[11]  T. Iwamoto,et al.  Angiotensin II inhibits interleukin-1 beta-induced nitric oxide production in cultured rat mesangial cells. , 1999, Kidney international.

[12]  D. Beasley.  COX-2 and cytosolic PLA2 mediate IL-1beta-induced cAMP production in human vascular smooth muscle cells. , 1999, The American journal of physiology.

[13]  D. Beasley.  COX-2 and cytosolic PLA2mediate IL-1β-induced cAMP production in human vascular smooth muscle cells. , 1999, American journal of physiology. Heart and circulatory physiology.

[14]  J. Fabiani,et al.  Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vessels of long-term cholesterol-fed rabbits. , 1999, Atherosclerosis.

[15]  Y. Toya,et al.  Mechanism of Angiotensin II-mediated Regulation of Fibronectin Gene in Rat Vascular Smooth Muscle Cells* , 1998, The Journal of Biological Chemistry.

[16]  E. Nishio,et al.  Aspirin and salicylate enhances the induction of inducible nitric oxide synthase in cultured rat smooth muscle cells. , 1998, Life sciences.

[17]  M. Murakami,et al.  The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release , 1998, The Journal of Biological Chemistry.

[18]  S. Marklund,et al.  Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[19]  Jullia A. Rosdahl,et al.  Regulation of 12-lipoxygenase by cytokines in vascular smooth muscle cells. , 1997, Hypertension.

[20]  U. Ikeda,et al.  Arginine vasopressin inhibits nitric oxide synthesis in cytokine-stimulated vascular smooth muscle cells. , 1997, Hypertension research : official journal of the Japanese Society of Hypertension.

[21]  A. Fukamizu,et al.  Stretch-induced MAP kinase activation in cardiomyocytes of angiotensinogen-deficient mice. , 1997, Biochemical and biophysical research communications.

[22]  L. Lanting,et al.  Platelet‐derived growth factor BB mediated regulation of 12‐lipoxygenase in porcine aortic smooth muscle cells , 1996, Journal of Cellular Physiology.

[23]  M. Yacoub,et al.  Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[24]  S. Srivastava,et al.  Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Carl Nathan,et al.  Nitric oxide synthases: Roles, tolls, and controls , 1994, Cell.

[26]  T. Tsuda,et al.  Expression of Nitric Oxide Synthase by Cytokines in Vascular Smooth Muscle Cells , 1994, Hypertension.

[27]  L. Lanting,et al.  Role of the Lipoxygenase Pathway in Angiotensin II–Induced Vascular Smooth Muscle Cell Hypertrophy , 1994, Hypertension.

[28]  H. Kolb,et al.  Nitric oxide production from macrophages is regulated by arachidonic acid metabolites. , 1993, Biochemical and biophysical research communications.

[29]  M. Yokoyama,et al.  Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells. Synergism with the induction elicited by inflammatory cytokines. , 1993, Journal of Biological Chemistry.

[30]  K. Ryoyama,et al.  Inhibition of macrophage nitric oxide production by arachidonate-cascade inhibitors , 1993, Cancer Immunology, Immunotherapy.

[31]  T. Tsuda,et al.  Cytokine‐induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cells , 1993, FEBS letters.

[32]  R. Busse,et al.  Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells , 1990, FEBS letters.

[33]  C. Glass,et al.  Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Steinberg,et al.  A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[35]  L. Lanting,et al.  Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model , 2002, Diabetologia.

[36]  八田 告.  Lowering of blood pressure improves endothelial dysfunction by increase of nitric oxide production in hypertensive rats , 2002 .

[37]  M. Lapointe,et al.  Phospholipase A2 metabolites regulate inducible nitric oxide synthase in myocytes. , 1998, Hypertension.

[38]  J. Berliner,et al.  The role of oxidized lipoproteins in atherogenesis. , 1996, Free radical biology & medicine.