Dexamethasone Inhibits Nitric Oxide Synthase mRNA Induction by Interleukin-la and Tumor Necrosis Factor-α in Vascular Smooth Muscle Cells

Marumo, Takeshi; Nakaki, Toshio; Nagata, Kiyoshi; Miyata, Masaaki; Adachi, H.; Esumi, Hiroyasu; Suzuki, Hiromichi; Saruta, Takao; Kato, Ryuichi

doi:10.1254/jjp.63.361

Cited by 17 publications

(6 citation statements)

References 22 publications

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“…However, the true mechanism is still unknown. Many studies have shown that a synergistic action of IL-1b, IFN-g , TNF-a and LPS on iNOS expression was observed in smooth muscle cells and other cells (26,27). Thus, we speculate that the discrepancy of iNOS expression by amlodipine may be due to treatment with different stimulators or combination of cytokines and LPS, and some unknown mechanisms are involved in the effect of amlodipine on NO synthesis.…”

Section: +mentioning

confidence: 78%

Amlodipine Inhibits Pro-inflammatory Cytokines and Free Radical Production and Inducible Nitric Oxide Synthase Expression in Lipopolysaccharide / Interferon-γ-Stimulated Cultured Vascular Smooth Muscle Cells

Chou

Yang

Pei

2002

Japanese Journal of Pharmacology

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ABSTRACT-Overproduction of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is importantly involved in the pathogenesis of endotoxemia and atherosclerosis. Calcium antagonists are commonly used as cardiovascular drugs and have a beneficial effect on prolonging survival in various models of endotoxin shock. The present study was to investigate the effect of a calcium antagonist amlodipine on nitrite, tumor necrosis factor-a (TNF-a ) and interleukin-1b (IL-1b) formation and iNOS induction both in lipopolysaccharide (LPS) and interferon-g (IFN-g)-treated rat aortic smooth muscle cells (RASMC) and in a rat model of endotoxemia. Incubation with amlodipine (0.1 -10 m M) for 24 h resulted in a significant and dose-dependent attenuation in medium nitrite, TNF-a and IL-1b formation as well as iNOS protein expression in LPS /IFN-g -treated RASMC. In addition, amlodipine inhibited leucigenin-induced superoxide formation in RASMC. In the rat endotoxic model, the serum nitrite /nitrate, TNF-a and IL-1b levels as well as iNOS protein expression of lungs were also suppressed by administration of amlodipine (50 m g/kg, i.v.). These results suggest that amlodipine may exert vascular beneficial effects by suppressing pro-inflammatory cytokines and free radical generation as well as iNOS induction in smooth muscle cells during activation of inflammatory mechanism.

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Section: +mentioning

confidence: 78%

Amlodipine Inhibits Pro-inflammatory Cytokines and Free Radical Production and Inducible Nitric Oxide Synthase Expression in Lipopolysaccharide / Interferon-γ-Stimulated Cultured Vascular Smooth Muscle Cells

Chou

Yang

Pei

2002

Japanese Journal of Pharmacology

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“…Griendling, Emory University, Atlanta, Ga) 22 or the cDNA probe specific for mouse 18S rRNA, the blots were washed, exposed to x-ray film, and analyzed with a densitometer as described previously. 10,23 The values obtained from blots hybridized with the p22 phox cDNA were corrected using the values obtained with the 18S rRNA probe and were expressed as a percentage of control.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Glucocorticoids Inhibit Superoxide Anion Production and p22 Phox mRNA Expression in Human Aortic Smooth Muscle Cells

et al. 1998

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Abstract-Recent reports suggest that the increased production of reactive oxygen species (ROS) in the vascular wall may contribute to the functional and structural changes associated with hypertension and atherosclerosis. Although glucocorticoid therapy can promote atherosclerosis, protective effects of these compounds on vascular lesion formation have been reported. In the present study, we investigated whether ROS production in cultured human aortic smooth muscle cells (HSMCs) can be modulated by glucocorticoids. Pretreatment of HSMCs with dexamethasone for 24 hours attenuated the basal and platelet-derived growth factor (PDGF)-AB-and angiotensin II-induced superoxide anion (O 2 ⅐ Ϫ ) production. PDGF-AB-stimulated O 2 ⅐ Ϫ production was also inhibited by prednisolone and hydrocortisone but not by other steroids, such as testosterone and norgestrel. Incubation of HSMCs with glucocorticoids for 24 hours decreased 2Ј,7Ј-dichlorodihydrofluorescein (DCHF) oxidation, an indicator of intracellular ROS levels. Dexamethasone decreased the mRNA expression of p22 phox, one of the components of NADPH oxidase, but had no effect on the activity of superoxide dismutase. The effects of dexamethasone on DCHF oxidation, and p22 phox mRNA expression and PDGF-AB-stimulated O 2 ⅐ Ϫ production were inhibited by the glucocorticoid receptor antagonist RU486. These results indicate that glucocorticoids decrease O 2 ⅐ Ϫ production by HSMCs via a receptor-dependent pathway. This effect is likely to be mediated by a decrease in the generating system, such as downregulation of p22 phox mRNA, rather than an increased inactivation of O 2 ⅐ Ϫ . The inhibition of ROS production might contribute to the local protective effects that glucocorticoids have on vascular lesion formation. (Hypertension. 1998;32:1083-1088.)

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“…After incubation with or without reagents for indi cated times, total RNA was extracted from the cells by a previously described method [17], RNA was applied to 1.2% formaldehyde-agarose gels and, after electro phoresis, transferred onto Biodyne nylon membranes (Pall BioSupport, East Hills, N.Y.) as previously de scribed [18]. A 700-bp fragment of the 5'-portion of cloned rat liver iNOS cDNA [19], a 0.9-kb NcolHindUl cDNA fragment of rat liver GTP:CHI [20], and the GAPDH cDNA probe were labeled by the ran dom-priming method with [a-32P]deoxy-CTP (Amersham Japan, Tokyo) as previously described [18].…”

Section: Rna Extraction and Northern Blot Analysismentioning

confidence: 99%

“…A 700-bp fragment of the 5'-portion of cloned rat liver iNOS cDNA [19], a 0.9-kb NcolHindUl cDNA fragment of rat liver GTP:CHI [20], and the GAPDH cDNA probe were labeled by the ran dom-priming method with [a-32P]deoxy-CTP (Amersham Japan, Tokyo) as previously described [18]. The specific activity of the radiolabeled probe was >3.0 x 105cpm/ng.…”

Section: Rna Extraction and Northern Blot Analysismentioning

confidence: 99%

Endothelin-1 Inhibits Induction of Nitric Oxide Synthase and GTP Cyclohydrolase I in Rat Mesangial Cells

Hirahashi

Nakaki²,

Hishikawa³

et al. 1996

Pharmacology

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To investigate the interaction between endothelin (ET) and the nitric oxide system, we examined the effects of ET-1 and ET-3 on the induction of inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GTP:CHI), the rate-limiting enzyme of de novo synthesis of the cofactor tetrahydrobiopterin (BH4), in rat mesangial cells. ET-1 inhibited the nitrite accumulation induced by a combination of interleukin-1β, tumor necrosis factor-α, and lipo-polysaccharide in a concentration-dependent manner. The inhibitory effect of ET-3 was less potent than that of ET-1. A selective ET_A antagonist, BQ-485, and an ET_A and ET_B antagonist, TAK-044, abolished the inhibitory effects of ET-1, whereas the selective ET_B antagonist BQ-788 had no effect on the inhibition produced by ET-1. These observations indicate that ET-1 inhibits cytokine-stimulated nitrite accumulation through the ET_A receptor. Western blot analysis showed that the suppression of nitrite accumulation was accompanied by a decrease in iNOS protein. Northern blot analysis showed that ET-1 inhibited the expression of both iNOS and GTP: CHI mRNA. In conclusion, ET-1 inhibits cytokine-stimulated nitric oxide production through the ET_A receptor by suppressing the expression of iNOS and GTP: CHI mRNA in rat mesangial cells.

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Dexamethasone Inhibits Nitric Oxide Synthase mRNA Induction by Interleukin-la and Tumor Necrosis Factor-α in Vascular Smooth Muscle Cells

Cited by 17 publications

References 22 publications

Amlodipine Inhibits Pro-inflammatory Cytokines and Free Radical Production and Inducible Nitric Oxide Synthase Expression in Lipopolysaccharide / Interferon-γ-Stimulated Cultured Vascular Smooth Muscle Cells

Amlodipine Inhibits Pro-inflammatory Cytokines and Free Radical Production and Inducible Nitric Oxide Synthase Expression in Lipopolysaccharide / Interferon-γ-Stimulated Cultured Vascular Smooth Muscle Cells

Glucocorticoids Inhibit Superoxide Anion Production and p22 Phox mRNA Expression in Human Aortic Smooth Muscle Cells

Endothelin-1 Inhibits Induction of Nitric Oxide Synthase and GTP Cyclohydrolase I in Rat Mesangial Cells

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