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.
Hashimoto
Tatsuo
T
Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
Kihara
Minoru
M
Yokoyama
Keiko
K
Fujita
Takayuki
T
Kobayashi
Syun-ichi
S
Matsushita
Kei
K
Tamura
Kouichi
K
Hirawa
Nobuhito
N
Toya
Yoshiyuki
Y
Umemura
Satoshi
S
D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002478:Cells, Cultured; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D054501:Group II Phospholipases A2; D007375:Interleukin-1 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates
D062365:Aminobenzoates; D002723:Chlorobenzoates; D002934:Cinnamates; D016861:Cyclooxygenase Inhibitors; D044950:Flavanones; D005419:Flavonoids; D007375:Interleukin-1; D016859:Lipoxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D062367:ortho-Aminobenzoates; D009569:Nitric Oxide; C006680:baicalein; D009637:Masoprocol; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D008084:Lipoxygenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2