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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the L-arginine-NO pathway on the formation of PGE2 by cultured astroglial cells incubated with the HIV coating glycoprotein gp120 was investigated. Preincubation of human cultured T 67 astrocytoma cells with gp 120 (100-500 nM) produced a significant increase of nitrite (the breakdown product of NO) and PGE2 in cell supernatants. The effect of gp 120 on both nitrite and PGE2 production was antagonized by inhibition of NO synthase by L-NAME (20-300 microM). The inhibition of gp120-induced PGE2 production by L-NAME was reverted by addition of arachidonic acid (30 microM), an effect antagonized by the cyclo-oxygenase inhibitor indomethacin (10 microM). Methylen bleu, an inhibitor of the biological activity of NO acting at the guanylate cyclase level failed to affect gp 120-mediated PGE2 release showing that the increase of cGMP subsequent to NO production was not involved in the modulatory activity of NO on arachidonic acid cascade. On the basis of present experiments we conclude that gp-120-induced release of PGE2 by astroglial cells is driven by NO, thereby contributing in the involvement of glial cells in HIV-related cerebral disorders.
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PMID:HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation. 752 Nov 67

Since early growth response-1 (Egr-1) is required for macrophage differentiation and nitric oxide (NO) is immunosuppressive, we hypothesized that NO would reduce Egr-1 expression in rat lung macrophages. The inflammatory stimuli interferon-gamma and lipopolysaccharide induced an early, transient increase in Egr-1 mRNA (> 5-fold at 2 h) and a sustained, high level of inducible NO synthase mRNA (> 100-fold from 4 to 24 h). The NO metabolites nitrite and nitrate rose > 10-fold in medium from stimulated versus unstimulated cells over 24 h. Concomitant with elevated nitrogen oxides, Egr-1 mRNA levels declined to 80% below unstimulated cells at 24 h. This decline was blocked by an inhibitor of NO production, NG-monomethyl-L-arginine. Further, the NO donor S-nitroso-N-acetylpenicillamine inhibited Egr-1 expression in a dose-dependent manner, producing complete inhibition at 0.5 mM. The effect of S-nitroso-N-acetylpenicillamine was not due to reduced macrophage viability. We conclude that Egr-1 induction precedes inducible NO synthase induction in stimulated rat macrophages and that subsequent NO production reduces macrophage expression of Egr-1. We propose that this mechanism is used to regulate macrophage differentiation in human immunodeficiency virus infection and other inflammatory states.
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PMID:Nitric oxide reduces early growth response-1 gene expression in rat lung macrophages treated with interferon-gamma and lipopolysaccharide. 752 82

The effect of the HIV coating glycoprotein gp 120 on the generation of NO by human cultured T67 astrocytoma cells was investigated. Preincubation of astrocytoma cells with gp 120 (10 pM, 100 and 500 nM) produced a significant, dose-dependent increase of nitrite levels in supernatant of pretreated cells which was higher when compared to untreated cells. This effect was prevented by coincubation of cells with monoclonal antibodies directed against gp 120, or by pretreatment of cells with the selective NO synthase inhibitor L-NAME (100 microM). The rise of nitrite following pretreatment of astrocytoma cells with gp 120 was accompanied by an increase in NO synthase activity which was mainly Ca(++)-independent. Also this effect was inhibited by antibodies against gp 120, showing the specificity of the activation of the L-Arg-NO pathway subsequent to incubation of astrocytoma cells with the HIV coating protein. In conclusion, the present results are consistent with an activation of the inducible, Ca(++)-independent isoform of NO synthase in cultured astrocytoma cells following coincubation with gp 120. This may contribute to explain some of the neuropathological changes accompanying HIV-related cognitive disorders.
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PMID:HIV gp120 glycoprotein stimulates the inducible isoform of no synthase in human cultured astrocytoma cells. 768 36

Cryptococcus neoformans is responsible for pulmonary and meningal infections in HIV patients. The lack of effective cellular cooperation caused by the low level of CD4+ cells, and the resistance of C. neoformans to phagocytosis allows growth and persistence of the yeast in the host. We describe here an in-vitro model of intracellular replication of C. neoformans inside J774-A.1 macrophages, and the determination of the intracellular antifungal activity of amphotericin B and fluconazole alone or in association with IFN-gamma. The maximum inhibitory effect was observed with one MIC of amphotericin B and 100 or 1000 IU/mL of IFN-gamma. amphotericin B alone (at 1 x MIC), or either 1 x or 50 x MIC of fluconazole in normal or IFN-gamma activated macrophages, did not eradicate the ingested yeast. A potential underlying mechanism of the synergy of amphotericin B in IFN-gamma primed macrophages was investigated by measurement of nitrite level and by use of the NO synthase competitive inhibitor, NG-monomethyl L-arginine (NMMA). One MIC of amphotericin B was able to activate the synthesis of nitrogen reactive intermediates in IFN gamma-primed macrophages. NMMA treated infected macrophages responded less well to IFN-gamma priming, resulting in a moderate inhibition in subsequent amphotericin B exposure.
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PMID:Synergic inhibitory activity of amphotericin-B and gamma interferon against intracellular Cryptococcus neoformans in murine macrophages. 773 Feb 21

Astrocytes are glial cells able to release nitric oxide (NO) under basal conditions as well as following different neurochemical stimuli including cytokines, endotoxins and soluble antigens, thereby participating in neuroimmune responses. In particular, the inducible isoform of NO synthase seems to be activated during co-incubation of this cell type with cytokines as well as in the presence of the HIV coating gp120 glycoprotein, an effect which is associated with an enhancement of prostanoid release. This seems also to occur via activation of cyclooxygenase by NO. Thus, the L-arginine-NO pathway found in astrocytes may represent a novel approach in the treatment of neuroimmune disorders such as multiple sclerosis, Alzheimer's disease and AIDS.
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PMID:Release of nitric oxide from astroglial cells: a key mechanism in neuroimmune disorders. 874 14

Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.
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PMID:Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. 894 6

Brain prostanoid levels are normally low but can increase after ischemia and during inflammatory and infectious diseases. High prostanoid levels can affect brain function in several ways. In particular, prostaglandin E2 (PGE2) might exert both immunodepressive and proinflammatory actions. The present short review focuses on the regulation of prostanoid synthesis in microglial cultures and on the possible role of PGE2 in the down-regulation of microglial activation induced by lipopolysaccharide (LPS). Our studies were carried out using purified mouse or rat microglial cultures. LPS induced a dose-dependent expression of the inducible isoform of cyclooxygenase (COX-2), both in neonatal and adult microglial cultures. In the latter, the inducibility of COX-2 increased with time in culture, paralleling the acquisition of a more 'activated' microglial phenotype, and appeared to account for the time-dependent increase in the PGE2/TXB2 production ratio. The LPS-induced COX-2 expression and prostanoid production were down-regulated by potentially neurotoxic agents, such as nitric oxide (NO), the proinflammatory cytokine IFN-gamma (which acted both directly and indirectly, through its NO-inducing activity) and the HIV regulatory protein tat. On the other hand, COX-2 expression was up-regulated by the macrophage-deactivating cytokine TGF-beta 1, by exogenous PGE2 itself, which acted through EP2 receptors linked to cyclic AMP generation, and by non steroidal anti-inflammatory drugs. Interestingly, PGE2 utilized the same EP2 receptor-mediated signal transduction mechanism to down-regulate the expression of the inducible NO synthase and the production of NO. Largely, but not exclusively, through its effect on cyclic AMP, PGE2 can also: i) depress the expression of major histocompatibility complex class II antigens and of the costimulatory molecule B7-2; ii) down-regulate TNF and up-regulate IL-10 microglial production; iii) inhibit microglial IL-12 secretion. These observations, together with literature data on in vivo models of central nervous system (CNS) diseases, suggest a neuroprotective role of PGE2 in pathological conditions.
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PMID:Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. 989 49

Increased levels of serum IgE have been described in HIV-1 infection; however, mechanisms implicated in this immunoglobulin production remain unknown. In this study, we demonstrate that in vitro infection of human peripheral blood mononuclear cells (PBMCs) by HIV-1 monocytotropic (Ba-L) or lymphocytotropic (LAI) strains promotes IL-4-induced IgE production, indicating that the HIV-1 infectious process may participate in the IgE production observed in vivo. The effect of membrane glycoproteins (gp160, gp120, and gp41) was also evaluated. It was found that gp120 specifically potentiates in a dose-dependent manner IL-4-induced IgE production and does not affect IL-4-induced IgG, IgA, or IgM production. In these experiments, gp160 was also found to upregulate IL-4-induced IgE production, whereas gp41 was ineffective. This effect of gp120, gp160, and HIV-1 infection on IgE synthesis was not observed in the absence of IL-4. In the presence of IL-4, the inducing effect of gp120 appeared to be indirect because gp120 did not modify purified B lymphocyte IgE production after IL-4 and anti-CD40 monoclonal antibody stimulation. As HIV-1 infection is associated with alterations of PBMC redox metabolism, the role of nitric oxide (NO) in this IgE production by human PBMCs was evaluated. In the presence of a specific inhibitor of NO synthase pathways (L-NAME), IgE production induced by IL-4 and gp120 was abolished. Taken together, these data indicate that HIV-1 envelope glycoprotein gp120 (and gp160) specifically enhances IL-4-induced IgE production by normal human PBMCs, probably through the regulation of the nitric oxide pathway.
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PMID:Role of nitric oxide in the promoting effect of HIV type 1 infection and of gp120 envelope glycoprotein on interleukin 4-induced IgE production by normal human mononuclear cells. 1071 Feb 13

Nitric oxide (NO) has been reported to regulate NF-kappaB, one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli. NO has been suggested to induce or inhibit the activation of NF-kappaB, its effect depending, among others, on the cell type considered. In this review, the inhibitory effect of NO on NF-kappaB (and subsequent suppression of NF-kappaB-dependent gene expression) in glial cells is reported. In particular, exogenous and endogenous NO has been observed to keep NF-kappaB suppressed, thus preventing the expression of NF-kappaB-induced genes, such as inducible NO synthase itself or HIV-1 long terminal repeat. Furthermore, the possible molecular mechanisms of NO-mediated NF-kappaB inhibition are discussed. More specifically, NO has been reported to suppress NF-kappaB activation inducing and stabilizing the NF-kappaB inhibitor, IkappaB-alpha. On the other hand, NO may inhibit NF-kappaB DNA binding through S-nitrosylation of cysteine residue (i. e., Cys62) of the p50 subunit. As a whole, a novel concept that the balance of intracellular NO levels may control the induction of NF-kappaB in glial cells has been hypothesized.
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PMID:Nitric oxide: an inhibitor of NF-kappaB/Rel system in glial cells. 1082 56

Subjects with human immunodeficiency virus type 1 (HIV-1) infection display increased activity of the hypothalamo-pituitary-adrenal (HPA) axis, which may play a role in both HIV-related neurodegenerative processes and disease progression. It has been speculated that the HIV coat protein gp120 may be responsible for these changes, and previous experimental evidence in both transgenic and nontransgenic mice supports this view. We speculated that one of the effects of gp120 in the CNS is to act within the hypothalamus to affect both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), the principal regulators of HPA axis. We therefore administered i.p. gp120 (100 ng/rat) or vehicle to male Wistar rats and then detected Fos protein (an index of neuronal activation), CRH, and AVP immunoreactivity in the cellular compartments of the hypothalamic paraventricular nucleus (PVN). In addition, we tested the direct effect of various concentrations of gp120 on the release of CRH and AVP from rat hypothalamic explants maintained in vitro. Any modulation of gp120 effects by nitric oxide (NO) pathways was also sought by coadministering i.p. to rats or adding to the hypothalamic preparations the NO synthase inhibitor N(G)-methyl-l-arginine (l-NMMA). Gp120 induced the expression of Fos protein in both the parvo- and the magnocellular PVN, which was significantly attenuated by l-NMMA 10(-6) nM/L (P < 0.001 vs gp120 alone). Double immunochemistry showed costaining for Fos protein and CRH or AVP in the PVN following gp120; the number of double-labeled CRH and AVP cells for Fos protein was markedly reduced (P < 0.001) by coadministration of l-NMMA 10(-6) nM/L. In the in vitro studies, addition of gp120 to the hypothalamic explants in the dose range of 10 pM-1 nM resulted in a clear stimulation of both CRH and AVP release (P < 0.05-0.001 compared to control); in the presence of l-NMMA at 10-fold higher concentrations the stimulatory effect of gp120 on the release of both peptides was completely lost. It would therefore appear that gp120 activates CRH and AVP-producing neurons in the hypothalamic PVN and stimulates the release of both peptides in vitro via NO-dependent mechanisms. These findings, in line with previous evidence, further suggest that the increased activity of the HPA axis associated with HIV infection may be of central origin, due to the effects of gp120 on hypothalamic CRH and AVP release.
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PMID:Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide. 1108 2


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