Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection by human immunodeficiency virus (HIV) is followed in many cases by a clinically quiescent or latent phase that appears to continue as long as host antiviral defense is intact. This has raised the possibility that certain host susceptibility factors (i.e., environmental cofactors) might influence the progression of the disease. In this study we demonstrate that morphine can function to activate HIV/LTR-CAT fusion gene (HIV-long terminal repeat-chloramphenicol acetyltransferase) when transfected into undifferentiated human SH-SY5Y neuroblastoma cells. The stimulatory effect of morphine is amplified in SH-SY5Y cells that have been induced to differentiate first with phorbol 12-myristate 13-acetate (PMA) and is much less in cells differentiated with retinoic acid (RA). Morphine does not appreciably activate HIV/LTR-CAT expression in human MOLT-3 and other T cells. Morphine activation of HIV/LTR-CAT in the SH-SY5Y cells is not reversible by naltrexone and appears to involve a Fos/Jun signaling system. Our results suggest that narcotics such as morphine may lead to activation of latent HIV infection. This may be particularly important in tissues, such as brain, which can host latent HIV infection and which is uniquely damaged in patients with acquired immunodeficiency syndrome (AIDS) as evidenced by neuronal degeneration and dementia. We also predict that these findings may have important implications for the pathogenesis of AIDS, particularly in opiate drug abusers.
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PMID:Morphine-induced transactivation of HIV-1 LTR in human neuroblastoma cells. 225 36

The beta-chemokine RANTES has recently been implicated in the neuropathogenesis of the human immunodeficiency virus. Based upon previous studies of the effects of morphine on microglial cell production of cytokines and chemotaxis towards the activated complement component C5a, we tested the hypothesis that this opiate would alter the production of and migration towards RANTES by human microglia. Treatment of highly purified microglial cell cultures with morphine (10(-8)-10(-6) M) potently inhibited RANTES production by lipopolysaccharide- and interleukin-1beta-stimulated cells. Using a chemotaxis chamber to assess directed migration towards RANTES, treatment of microglial cells with morphine (10(-10)-10(-6) M) was found to suppress chemotaxis. The inhibitory effects of morphine on RANTES production and on chemotaxis were blocked by naloxone and beta-funaltrexamine, indicating that morphine mediated its suppressive effects via activation of microglial p-opioid receptors. Morphine's inhibitory effect on chemotaxis did not appear to be associated with an alteration in RANTES-induced [Ca2+]i mobilization. While the clinical significance of these in-vitro findings is unknown, they suggest that mu-opioid receptor agonists could alter certain neurodegenerative and inflammatory processes within the brain.
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PMID:Morphine inhibits human microglial cell production of, and migration towards, RANTES. 1110 2

Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. These cultures were continuously treated with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat (1-72) protein, a non-neurotoxic HIV-1 Tat deletion mutant (TatDelta31-61) protein, or immunoneutralized HIV-1 Tat (1-72) protein. Neuronal and astrocyte viability was examined by ethidium monoazide exclusion, and by apoptotic changes in nuclear heterochromatin using Hoechst 33342. Morphine (10nM, 100nM or 1microM) significantly increased Tat-induced (100 or 200nM) neuronal losses by about two-fold at 24h following exposure. The synergistic effects of morphine and Tat were prevented by naloxone (3microM), indicating the involvement of opioid receptors. Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia.
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PMID:Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. 1122 93

Opiate addiction has been reported to contribute to the progression of renal injury. In addition, opiate addiction is a major risk factor for the development of human immunodeficiency virus-associated nephropathy. In the present study, we evaluated the effects of morphine, an active metabolite of heroin, on glomerular epithelial cell (GEC) growth and the involved molecular mechanism. At lower concentrations, morphine promoted GEC proliferation; however, at higher concentrations, morphine triggered apoptosis. Antioxidants inhibited morphine-induced proliferation as well as apoptosis. Similarly, free radical scavengers prevented morphine-induced GEC proliferation and apoptosis. Because proliferative and proapoptotic effects of morphine were inhibited by free radical scavengers as well as antioxidants, it appears that these effects of morphine are mediated through oxidative stress. Hemin, an inducer of heme oxygenase (HO) activity, inhibited GEC proliferation and promoted GEC apoptosis under basal and morphine-stimulated conditions. On the other hand, zinc protoporphyrin, an inhibitor of HO activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as well as morphine-stimulated conditions. These findings suggest that HO activity is directly related to GEC apoptosis and inversely related to GEC proliferation. Morphine, de novo, had bimodal effects on HO activity: lower concentrations increased and higher concentrations decreased HO activity. It appears that HO activity may be modifying morphine-induced GEC growth.
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PMID:Role of oxidative stress and heme oxygenase activity in morphine-induced glomerular epithelial cell growth. 1281 15

Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection. Because the direct effects of opiates on HIV infection are difficult to determine epidemiologically, animal models of lentivirus infection are relied upon to study the effects of opiates in the absence of confounding factors. Morphine, the predominant metabolite of heroin, is used in most experimental systems examining heroin abuse. In this study, morphine treatment of feline immunodeficiency virus (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed with withdrawals. Plasma cortisol levels were measured for evidence of stress associated with morphine withdrawal. In the morphine-treated cats, cortisol levels peaked at time points corresponding to morphine withdrawal and returned to baseline levels during treatment and several weeks after the final withdrawal. Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed cats did not experience enhanced severity of FIV-related disease; in fact, morphine demonstrated a protective effect on FIV-associated changes in brainstem auditory evoked potentials. Our research suggests that opiate exposure is unlikely to adversely affect the progression of acute lentivirus infection and might be beneficial in controlling associated neurological disease.
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PMID:Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers. 1463 69

This study was designed to assess the in vitro effects of morphine on the lymphocytes infected with SIV. CEM x174 cells were cotreated with morphine and simian immunodeficiency virus (SIVmac239). Cells were cultured for 96 h and the effects of morphine on the viability of infected cells were determined. At the concentration of 1 micromol/l, morphine could inhibit the proliferation of CEM x174 cells at the culture of 72 h. The stronger effect was observed in the case of viral infection. During 72 h SIV loading, the cells were accumulated in S phase in all SIV infected groups. The S arrest was observed in every experimental group and statistically different from normal groups (P<0.05). The results from annexin V binding assay showed that SIV infection resulted in a lower proportion of vital cells and higher mortality compared with corresponding control (P<0.01). Morphine failed to induce detectable alteration in the cell cycle profile of viral infected cells. Western blotting showed that the synthesis of intracellular p53 and bax protein was gradually up-regulated in the virus-loading period of 72 h. Naloxone had an apparent additive rather than antagonistic effect on the morphine-associated enhancement of bax expression. The ratio of bax/bcl-2 proteins appeared to tilt the balance toward apoptosis. At 72 h of infection, 1 micromol/l of morphine significantly elevated the level of caspase-3. These results indicated that the alteration in the balance of intracellular apoptotic and anti-apoptotic elements is one of the reasons of accelerated progression of acquired immunodeficiency syndrome (AIDS) by opioids abuse.
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PMID:Morphine aggravates the apoptosis of simian immunodeficiency virus infected CEM x174 cells in the prolonged culture in vitro. 1553 Dec 96

Recent evidence suggests that injection drug users who abuse heroin are at increased risk of CNS complications from human immunodeficiency virus (HIV) infection. Opiate drugs may intrinsically alter the pathogenesis of HIV by directly modulating immune function and by directly modifying the CNS response to HIV. Despite this, the mechanisms by which opiates increase the neuropathogenesis of HIV are uncertain. In the present study, we describe the effect of morphine and the HIV-1 protein toxin Tat(1-72) on astroglial function in cultures derived from ICR mice. Astroglia maintain the blood-brain barrier and influence inflammatory signaling in the CNS. Astrocytes can express mu-opioid receptors, and are likely targets for abused opiates, which preferentially activate mu-opioid receptors. While Tat alone disrupts astrocyte function, when combined with morphine, Tat causes synergistic increases in [Ca(2+)](i). Moreover, astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release, including monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin-6 (IL-6). Morphine-Tat interactions were prevented by the mu-opioid receptor antagonist beta-funaltrexamine, or by immunoneutralizing Tat(1-72) or substituting a nontoxic, deletion mutant (Tat(Delta31-61)). Our findings suggest that opiates may increase the vulnerability of the CNS to viral entry (via recruitment of monocytes/macrophages) and ensuing HIV encephalitis by synergistically increasing MCP-1 and RANTES release by astrocytes. The results further suggest that astrocytes are key intermediaries in opiate-HIV interactions and disruptions in astroglial function and inflammatory signaling may contribute to an accelerated neuropathogenesis in HIV-infected individuals who abuse opiates.
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PMID:Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. 1563 Jul 4

Opiates have profound effects on the function of human immune cells and are a possible cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease. We investigated the impact of morphine on CD8+ T cell-mediated, noncytotoxic, anti-HIV activity in latently infected human immune cells. Morphine inhibited the noncytotoxic, anti-HIV activity of CD8+ T cells in HIV latently infected cells (U1 and J1.1). Naltrexone abrogated the morphine-mediated, inhibitory effect on the noncytotoxic, anti-HIV activity of CD8+ T cells. Interferon-gamma (IFN-gamma), a potent antiviral cytokine produced by CD8+ T cells, was partially responsible for CD8+ T cell-mediated, noncytotoxic, anti-HIV activity. The anti-HIV activity of IFN-gamma was also compromised by morphine treatment. Further, morphine attenuated CD8+ T cell-mediated suppression of the HIV long-terminal repeat promoter activation. Morphine also inhibited CD8+ T cell-induced expression of the signal transducer and activator of transcription-1, an important transcriptional factor in the IFN signaling pathway. These data provide additional evidence to support the notion that opioids play a role in impairing the anti-HIV function of the immune system.
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PMID:Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells. 1600 Mar 93

A homeostatic balance exists between the cellular generation of oxidant species and endogenous antioxidants under normal physiological conditions. Human Immunodeficiency Virus (HIV) infection is known to affect this balance causing oxidative stress. However, the interaction of HIV infection with a substance abuse on cellular oxidant/antioxidant system is sparse. This study was designed in order to investigate the interactive effect of morphine abuse and Simian Immunodeficiency Virus/ Simian Human Immunodeficiency Virus (SIV/SHIV) infection on plasma oxidant/antioxidant balance in rhesus macaques. Six rhesus macaques adapted to morphine dependence (20 weeks) along with three controls were infected with mixture of SHIV(KU-1B), SHIV(89.6P), and SIV(17E-Fr). Plasma samples from morphine-dependent and control macaques were analyzed for an array of oxidative stress indices after 16 weeks of infection. Morphine-dependence significantly increased plasma malondialdehyde (MDA) and 8-isoprostane levels (8-fold and 2-fold), but these animals showed higher MDA and 8-isoprostane levels after viral infection (18-fold and 4-fold) which was directly correlated with increase in viral load and decline in CD4+ cells. Plasma glutathione (GSH) level depleted (55%) with morphine dependence that was further depleted (25%) by the infection. Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased by 30% and 110%, respectively with morphine dependence, but that was decreased by the infection. Catalase (CAT) activity declined (25%) with morphine dependence that was further declined by infection. Our results clearly suggest that morphine interaction with SIV/SHIV infection causes higher oxidative tissue injury that might have implication in the pathogenesis of AIDS in morphine-dependent macaques.
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PMID:Interaction of SIV/SHIV infection and morphine on plasma oxidant/antioxidant balance in macaque. 1793

Morphine is known to prevent the development of cell-mediated immune (CMI) responses and enhance expression of the CCR5 receptor in monocyte macrophages. We undertook a study to determine the effect of morphine on the neuropathogenesis and immunopathogenesis of simian immunodeficiency virus (SIV) infection in Indian Rhesus Macaques. Hypothetically, the effect of morphine would be to prevent the development of CMI responses to SIV and to enhance the infection in macrophages. Sixteen Rhesus Macaques were divided into three experimental groups: M (morphine only, n = 5), VM (morphine + SIV, n = 6), and V (SIV only, n = 5). Animals in groups M and VM were given 2.5 mg/kg of morphine sulfate, four times daily, for up to 59 weeks. Groups VM and V were inoculated with SIVmacR71/17E 26 weeks after the beginning of morphine administration. Morphine prevented the development of enzyme-linked immunosorbent spot-forming cell CMI responses in contrast to virus control animals, all of which developed CMI. Whereas morphine treatment had no effect on viremia, cerebrospinal fluid viral titers or survival over the time course of the study, the drug was associated with a tendency for greater build-up of virus in the brains of infected animals. Histopathological changes in the brains of animals that developed disease were of a demyelinating type in the VM animals compared to an encephalitic type in the V animals. This difference may have been associated with the immunosuppressive effect of the drug in inhibiting CMI responses.
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PMID:Effect of morphine on the neuropathogenesis of SIVmac infection in Indian Rhesus Macaques. 1824 28


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