Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages

Rosa, Massimo Di; Radomski, M. W.; Carnuccio, Rosa; Moncada, Salvador

doi:10.1016/0006-291x(90)91583-e

Cited by 435 publications

(191 citation statements)

References 19 publications

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“…Induction of NO synthase in macrophages is strongly inhibited by glucocorticoids such as dexamethasone and hydrocortisone (Di Rosa et al, 1990), probably acting at the level of transcription of mRNA. We confirmed that dexamethasone substantially inhibited nitrite and citrulline production in LPS-activated J774 cells (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Expression of this enzyme is time-dependent, known to involve de novo protein synthesis and can be inhibited by glucocorticoids such as dexamethasone (Di Rosa et al, 1990;Assreuy & Moncada, 1992). The sustained production of NO is critically dependent on the presence of extracellular arginine (Drapier & Hibbs, 1988;Granger et al, 1990;Takema et al, 1991;Bogle et al, 1992a;Assreuy & Moncada, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Baydoun

Bogle

Pearson

et al. 1993

British J Pharmacology

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1 Effects of dexamethasone on induction of nitric oxide (NO) synathase and L-arginine transport by lipopolysaccharide (LPS) were examined in a murine cultured macrophage cell line J774. Metabolism of L-arginine to L-citrulline and subsequent changes in intracellular amino acids pools were correlated with changes in nitrite production. 3 Induction of NO synthase by LPS (1 jig ml-', 24 h) alone was accompanied by a marked increase in arginine utilisation leading to decreased intracellular arginine levels and elevated intracellular and extracellular L-citrulline levels. These changes were further enhanced in the presence of interferon-y (IFN-y, 100 units ml-', 24h).4 Dexamethasone (1 jaM) abolished the increases in both nitrite and citrulline production induced by LPS alone but only partially reversed the combined effects of LPS and IFN-y. In contrast, treatment of cells with dexamethasone (10 jtM) had no effect on the LPS-mediated induction of arginine transport or the decrease in intracellular arginine concentration. 5 We conclude that induction of arginine transporter activity in LPS-stimulated J774 cells involves de novo synthesis of carrier proteins, which increases transport of exogenous arginine during enhanced NO production. Moreover, the intracellular signalling pathways mediating induction of arginine transport and of NO synthase by LPS in activated macrophages diverge, since only the latter is sensitive to dexamethasone.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Baydoun

Bogle

Pearson

et al. 1993

British J Pharmacology

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“…L-NIL is approximately 28-fold more selective for iNOS in comparison with the constitutive endothelial NOS isoform (49). Similarly, dexamethasone inhibits the induction of iNOS without affecting the constitutive isoforms (50,51). While the edema was more severe in the kidneys perfused with the addition of L-NAME, blockade of iNOS also leads to profound edema supporting the function of iNOS during organ culture.…”

Section: Discussionmentioning

confidence: 98%

NOS: The Underlying Mechanism Preserving Vascular Integrity and During Ex Vivo Warm Kidney Perfusion

Brasile

Stubenitsky

Booster

et al. 2003

American Journal of Transplantation

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Research involving metabolically active and functioning organs, maintained ex vivo in culture-like conditions, could provide numerous opportunities for medical innovations and research. We report successful perfusion of isolated canine and human kidneys ex vivo at near physiologic temperature for 48 h. During the perfusions parameters of metabolism and function remained stable. Nitric oxide synthase (NOS) was identified as the underlying mechanism preserving vascular integrity. Most importantly, when the canine kidneys were reimplanted there was immediate normal renal function. This report highlights the potential significance of whole organ culture using a warm temperature ex vivo perfusion and discusses medical applications that could be developed.

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“…and its final products nitrite NO ÿ 2 and nitrate NO ÿ 3 ) play an important role in cytostatic/cytotoxic actions of these cells [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Macrophage nitric oxide synthase (NOS) activation by Nocardia opaca fractions and 15- and 56-kD isolated antigens

Tučková

Zı́dek

Hanikýřová

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThe Gram-positive bacterium, Nocardia opaca, is a source of substances with adjuvant effect, ability to stimulate macrophages and natural killer cells for enhanced cytotoxity and cytokine production and B lymphocytes for polyclonal immunoglobulin secretion. We determined the immunogenicity of isolated N. opaca fractions and prepared MoAbs against immunogenic water-soluble mitogen (NWSM). Two main proteins of molecular mass 15 and 56 kD were detected in Western blot analysis and isolated by affinity chromatography using anti-NWSM MoAb B7/7. Both these isolated nocardial antigens were found to stimulate mouse peritoneal macrophage NOS. The effect of 5 ¹ g NWSM was comparable to that of 5 ¹ g lipopolysaccharide (LPS) or 20 U of interferon-gamma (IFN-°) added to cell cultures. The MoAb B7/7 decreased NO 2 ÿ production induced by NWSM or by isolated nocardial antigens, but did not significantly influence the production elicited by LPS or IFN-°. On the other hand, NOS activation by NWSM was not affected by anti-IFN-°MoAb. The possible independent pathway for IFN-°and NWSM macrophage activation is discussed.

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Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages

Cited by 435 publications

References 19 publications

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

NOS: The Underlying Mechanism Preserving Vascular Integrity and During Ex Vivo Warm Kidney Perfusion

Macrophage nitric oxide synthase (NOS) activation by Nocardia opaca fractions and 15- and 56-kD isolated antigens

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