Nitric Oxide Production by Murine Macrophages Is Inhibited by Prolonged Elevation of Cyclic AMP

Bulut, Vedat; Severn, Alison; Liew, Foo Y.

doi:10.1006/bbrc.1993.2162

Cited by 67 publications

(34 citation statements)

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“…The effect was dose dependent, with an IC 50 value of 100 nM, mediated via /3-adrenergic receptor stimulation and replicated by the cyclic AMP (cAMP) analogue dbcAMP. Our initial observations in astrocytes, one of the first to demonstrate that cAMP could be a suppressive modulator of NOS-2 expression, have recently been confirmed by a second group (Pahan et al, 1997), and suppressive effects of cAMP on NOS-2 expression have been described for several other cell types (Bulut et al, 1993;Raddassi et al, 1993;Messmer and Brune, 1994;Harbrecht et al, 1995;Andersen et al, 1996;Minghetti et al, 1997). In astrocytes, other neurotransmitters, including glutamate and ATP (Park et al, 1994;Murphy et al, 1995) and angiotensin II (Chandler et al, 1995), also decrease astroglial NOS-2 expression.…”

mentioning

confidence: 72%

“…Additionally, the ability of cAMP to block NOS-2 induction has been described several times. Initial reports showed that prostaglandins, which can elevate intracellular cAMP levels, reduced NOS-2 induction and that inhibitors of adenylate cyclase prevented prostaglandin effects (Marotta et al, 1992;Bulut et al, 1993;Raddassi et al, 1993;Harbrecht et al, 1996;Minghetti et al, 1997). More direct evidence that elevated cAMP levels can block NOS-2 induction comes from studies using lipophilic cAMP analogues (forskolin, dbcAMP) and /3-adrenergic agofists (isoproterenol) both in vitro (Raddassi et al, 1993;Messmer and Brune, 1994;Andersen et al, 1996;Minghetti et al, 1997) as well as in vivo (Szabo et al, 1997).…”

Section: Ill-/i Alonementioning

confidence: 99%

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Suppression of Astroglial Nitric Oxide Synthase Expression by Norepinephrine Results from Decreased NOS‐2 Promoter Activity

Feinstein

1998

Journal of Neurochemistry

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Abstract:We previously demonstrated that norepinephrifle (NE) inhibits induction of the calcium-independent isoform of nitric oxide synthase (NOS-2) in primary rat astrocyte cultures. However, the molecular mechanisms underlying this effect are unknown. In C6 cells and astrocytes, NE suppressed both cytokine-and lipopolysaccharide (LPS)-dependent nitrite accumulation, an index of NOS-2 activity. NE reduced the steady-state levels of NOS-2 mRNA induced by LPS plus cytokines but did not decrease NOS-2 mRNA stability or inhibit activation or subunit composition of transcription factor nuclear factor KB, which is necessary for NOS-2 induction. In 06 cells stably transfected with a 1 ‚588-bp mouse NOS-2 promoter, NE reduced LPS plus cytokine-induced reporter gene expression, suggesting inhibition of NOS-2 promoter activity. In contrast, suppression was lost when a truncated 85-bp NOS-2 promoter was used, and in these cells NE potentiated reporter gene expression, alone or in the presence of LPS and cytokines. These results suggest that the suppressive effects of NE are due to modification of transcription factor activity in a region located between -1,588 and -85 of the NOS-2 promoter and may help explain observations that in some cells cyclic AMP can potentiate, rather than suppress, NOS-2 expression.

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mentioning

confidence: 72%

Section: Ill-/i Alonementioning

confidence: 99%

Suppression of Astroglial Nitric Oxide Synthase Expression by Norepinephrine Results from Decreased NOS‐2 Promoter Activity

Feinstein

1998

Journal of Neurochemistry

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“…In addition, hydrogen peroxide, one of the reactive oxygen species, is known to stimulate H 4 B synthesis in vascular endothelial cells (Shimizu et al, 2003). Moreover, PGE2 may also play important roles in functional activation of iNOS enzyme through its receptorligated signaling mediated by a cAMP (Bulut et al, 1993;Chen et al, 1999). PGE2 has been shown to increase intracellular cAMP in gastric mucosal cells (Hiraishi et al, 1986).…”

Section: Effect Of Cox Activity On No Production By Inos 999mentioning

confidence: 99%

“…Several studies focused on this point have been performed by the application of either COX inhibitors or PGE2 to in vivo or in vitro investigations (Bulut et al, 1993;Amin et al, 1995;Chen et al, 1999;Galea and Feinstein, 1999; Boje et al, Immunostaining for iNOS in the intact gastric mucosa (A) and 6 h after exposure to LPS (B). Immunostaining for COX-2 in the intact gastric mucosa (C) and 6 h after exposure to LPS (D) (original magnification, 400ϫ).…”

Section: Effect Of Cox Activity On No Production By Inos 999mentioning

confidence: 99%

In Vivo Study on Cross Talk between Inducible Nitric-Oxide Synthase and Cyclooxygenase in Rat Gastric Mucosa: Effect of Cyclooxygenase Activity on Nitric Oxide Production

Uno

Iuchi

Fujii

et al. 2004

J Pharmacol Exp Ther

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The integrity of gastric mucosa during endotoxemia is maintained by the balance of inflammatory mediators, such as prostanoids originated from cyclooxygenase-2 (COX-2) and nitric oxide (NO) from inducible nitric-oxide synthase (iNOS). Thus, we elucidated in vivo cross talk between prostanoids and NO in gastric mucosa during endotoxemia, using an iNOS-specific inhibitor, N-(3-(aminomethyl)benzyl)acetamidine (1400W); a nonspecific COX inhibitor, indomethacin; and a COX-2-specific inhibitor, N-(2-[cyclohexyloxy]-4-nitrophenyl)methanesulfonamide (NS-398). Gastric mucosal NO and prostaglandin E2 (PGE2), a predominant product of COX, expressed as mean Ϯ S.D. of five rats per group, were assayed by electron paramagnetic resonance spectrometry and enzyme immunoassay technique, respectively. The levels of NO and PGE2 increased gradually up to 6 h after administration of bacterial lipopolysaccharide (LPS) (NO: control, 0.35 Ϯ 0.16; 6 h, 13.3 Ϯ 3.3 nmol/g tissue/30 min; and PGE2: control, 288 Ϯ 16; 6 h, 806 Ϯ 15 pg/g tissue). Pretreatment with 1400W decreased the increase in NO level without any effect on the PGE2 level (NO, 4.0 Ϯ 0.4 nmol/g tissue/30 min; PGE2, 788 Ϯ 26 pg/g tissue). In contrast, treatment with indomethacin and NS-398 inhibited not only PGE2 level but also NO level in a dose-dependent manner without any significant effect on both iNOS and COX protein and mRNA expression. These results demonstrate that in the LPStreated rat gastric mucosa, PGE2 enhances the release of NO after activation of iNOS, although NO produced by iNOS does not stimulate the release of PGE2 by COXs. The effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammatory states.

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“…The intracellular signals that regulate the expression of iNOS have been only partially characterized in a small number of cell types. Increases in intracellular cyclic AMP levels enhanced interferon (IFN)-induced NOS expression in vascular smooth muscle cells [4] but partially reduced lipopolysaccharide (LPS)-and IFN-induced NO' production in murine macrophages [5]. Protein kinase C appears to be involved with iNOS expression in *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Potent inhibition of inducible nitric oxide synthase by geldanamycin, a tyrosine kinase inhibitor, in endothelial, smooth muscle cells, and in rat aorta

1997

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We have examined whether specific protein tyrosine kinase (PTK) inhibitors (genistein, tyrphostin, or geldanamycin) prevent nitric oxide (NO') production in rat smooth muscle cells (SMC), in murine brain endothelial cells (MBE), and in isolated rat aortas treated with endotoxin (LPS) and/or cytokines. Tyrphostin failed to inhibit either the release of nitrite in both endothelial and smooth muscle cells or vascular hyporeactivity in rat aorta, caused by immunostimulants. Genistein decreased nitrite production in MBE only at high concentration but had no effect on nitrite production in SMC and on the hypocontractility in aortic rings. In contrast, low concentrations of geldanamycin abolished the release of nitrite in MBE and in SMC treated with endotoxin and/or cytokines. Geldanamycin inhibited also the hypocontractility to phenylephrine in aortic rings treated with LPS or interleukin-1. This inhibitor failed to inhibit the release of nitrite and the vascular hyporeactivity once nitric oxide synthase (NOS) was induced by immunostimulants whereas methyl-L-arginine, an inhibitor of NOS, had significant effects. These data suggest that LPS-and cytokines-induced NO" production initiate a common signaling pathway involving a PTK that is inhibited by geldanamycin but not or slightly by tyrphostin or genistein at a point that precedes the induction of NOS.

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Nitric Oxide Production by Murine Macrophages Is Inhibited by Prolonged Elevation of Cyclic AMP

Cited by 67 publications

References 0 publications

Suppression of Astroglial Nitric Oxide Synthase Expression by Norepinephrine Results from Decreased NOS‐2 Promoter Activity

Suppression of Astroglial Nitric Oxide Synthase Expression by Norepinephrine Results from Decreased NOS‐2 Promoter Activity

In Vivo Study on Cross Talk between Inducible Nitric-Oxide Synthase and Cyclooxygenase in Rat Gastric Mucosa: Effect of Cyclooxygenase Activity on Nitric Oxide Production

Potent inhibition of inducible nitric oxide synthase by geldanamycin, a tyrosine kinase inhibitor, in endothelial, smooth muscle cells, and in rat aorta

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