Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria, but also host cells by inactivation of enzymes leading to cell death. The actions of all forms of NOS are mediated not only by the free radical oxidant properties of this soluble gas, but also by its activation of guanylate cyclase (GC), leading to the production of cyclic guanosine monophosphate (cGMP) that mediates many of its physiological actions. In addition, NO activates cyclooxygenase and lipoxygenase, leading to the production of physiologically relevant quantities of prostaglandin E2 (PGE2) and leukotrienes. In the case of iNOS, the massive release of NO, PGE2, and leukotrienes produces toxic effects. Systemic injection of LPS causes induction of interleukin (IL)-1 beta mRNA followed by IL-beta synthesis that induces iNOS mRNA with a latency of two and four hours, respectively, in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier, and shortly thereafter, in hypothalamic regions, such as the temperature-regulating centers, paraventricular nucleus containing releasing and inhibiting hormone neurons, and the arcuate nucleus, a region containing these neurons and axons bound for the median eminence. We are currently determining if LPS similarly activates cytokine and iNOS production in the cardiovascular system and the gonads. Our hypothesis is that recurrent infections over the life span play a significant role in producing aging changes in all systems outside the blood-brain barrier via release of toxic quantities of NO. NO may be a major factor in the development of coronary heart disease (CHD). Considerable evidence has accrued indicating a role for infections in the induction of CHD and, indeed, patients treated with a tetracycline derivative had 10 times less complications of CHD than their controls. Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion. Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone, melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. iNOS induction in the paraventricular nucleus may cause the decreased nocturnal secretion of growth hormone (GH) and prolactin that occurs with age, and its induction in the arcuate nucleus may destroy luteinizing hormone-releasing hormone (LHRH) neurons, thereby leading to decreased release of gonadotropins. Recurrent infections may play a role in aging of other parts of the brain, because there are increased numbers of astrocytes expressing IL-1 beta throughout the brain in aged patients. IL-1 and products of NO activity accumulate around the plaques of Alzheimer's, and may play a role in the progression of the disease. Early onset Parkinsonism following flu encephalitis during World War I was possibly due to induction of iNOS in cells adjacent to substantia nigra dopaminergic neurons leading to death of these cells, which, coupled with ordinary aging fall out, led to Parkinsonism. The central nervous system (CNS) pathology in AIDS patients bears striking resemblance to aging changes, and may also be largely caused by the action of iNOS. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play an important acute and chronic role in reducing or eliminating the oxidant damage produced by NO.
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PMID:The nitric oxide hypothesis of aging. 995 25

The Tat protein of HIV-1, a transactivator of viral gene expression, is released by acutely infected T cells and, in this form, exerts angiogenic activities. These have linked the protein to the pathogenesis of Kaposi's sarcoma (KS), a vascular tumor frequent and aggressive in HIV-1-infected individuals (AIDS-KS). In this study, we show that a combination of the same inflammatory cytokines increased in KS lesions, namely IL-1 beta, TNF-alpha, and IFN-gamma, synergizes with Tat to promote in nude mice the development of angioproliferative KS-like lesions that are not observed with each factor alone. Inflammatory cytokines induce the tissue expression of both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), two angiogenic molecules highly produced in primary KS lesions. However, bFGF, but not VEGF, synergizes with Tat in vivo and induces endothelial cells to migrate, to adhere, and to grow in response to Tat in vitro. Tat angiogenic effects correlate with the expression of the alpha v beta 3 integrin that is induced by bFGF and binds the arginine-glycine-aspartic acid (RGD) region of Tat. In contrast, no correlation is observed with the expression of alpha v beta 5, which is promoted by VEGF and binds Tat basic region. Finally, KS lesion formation induced by bFGF and Tat in nude mice is blocked by antagonists of RGD-binding integrins. Because alpha v beta 3 is an RGD-binding integrin that is highly expressed in primary KS lesions, where it colocalizes with extracellular Tat on vessels and spindle cells, these results suggest that alpha v beta 3 competitors may represent a new strategy for the treatment of AIDS-KS.
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PMID:Inflammatory cytokines synergize with the HIV-1 Tat protein to promote angiogenesis and Kaposi's sarcoma via induction of basic fibroblast growth factor and the alpha v beta 3 integrin. 1043 28

Toxplasma gondii is an intracellular protozoan parasite which invades various organs including the central nervous system. Immunity is crucial for preventing development of toxoplasmic encephalitis (TE) following infection. IFN-gamma-mediated immune response plays a central role in the resistance. The activation of microglia and astrocytes by IFN-gamma or a combination of this cytokine with TNF-alpha appears to be an important effector mechanism in the host immunity. GM-CSF, IL-1 beta and IL-6 may participate in this activation. iNOS is a molecule which mediates the protective activity of the activated murine microglia and human astrocytes; however, another unknown mechanism(s) not mediated by iNOS is involved in the activity of activated murine astrocytes and human microglia. IL-6 plays a protective role, at least in part, by up-regulating IFN-gamma production during the chronic stage of infection in mice. IL-6 also plays a role in regulating the infiltration of T cell subsets into the brain. IL-4 appears to play a protective role, but its role may differ depending on the strains of mice. In contrast to these protective cytokines, IL-10 may play a pathogenic role by down-regulating IFN-gamma production. The resistance against development of TE is under genetic control in both mice and humans. The Ld gene within the D region of the H-2 complex confers resistance in mice. In AIDS patients, HLA-DQ3 appears to be a genetic marker of susceptibility, and HLA-DQ1 appears to be a resistance marker. Strains (genetic variation) of T. gondii is another factor which affects the susceptibility of the host to the development of TE. The genotypes of the parasite may be important for determining the susceptibility. It is possible that the genes of the host and genetic variation of T. gondii affect immune response of the host to the parasite, and thereby contribute to determining the resistance against the development of TE.
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PMID:Genes, cells and cytokines in resistance against development of toxoplasmic encephalitis. 1063 75

Loss of periodontal support and eventually tooth loss is a common finding among acquired immunodeficiency syndrome (AIDS) patients. The cause of this destruction may be an increase in periodontal disease activity at sites within the same individual and also may be related to an increase in the pro-inflammatory cytokines, diffused through the gingival crevicular sulcus in AIDS patients. A study was undertaken to determine the relative levels of the pro-inflammatory cytokines, interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha), in gingival crevicular fluid collected from the deep (> 5 mm periodontal pocket depth) and shallow (< or = 3 mm periodontal pocket depth) periodontal pockets of 39 HIV-1-infected patients and 20 age-, race- and sex-matched uninfected controls. Complete medical history including risk factors such as intravenous drug abuse was taken. Gingival crevicular fluid samples were collected on periopaper strips. Cytokines were estimated by solid-phase enzyme-linked immunosorbent assay. To assess the degree of HIV activity, the viral load of these patients was determined by an Amplicor HIV-1 monitor kit using reverse transcriptase polymerase chain reaction. Gingival crevicular fluid from HIV-1-infected patients showed a two-fold increase in both IL-1 beta and TNF-alpha in deep periodontal pockets in comparison to shallow pockets, whereas IL-6 increased 1.8-fold. There was a significant (P < 0.05) increase in IL-1 beta, IL-6 and TNF-alpha in gingival crevicular fluid (both shallow and deep pockets) from HIV-1-infected patients in comparison to uninfected controls and also significantly elevated in deep versus shallow pockets in these patients. Although IL-1 beta, L-6 and TNF-alpha levels among HIV-1-infected patients with a high viral load (> 10,000 copies/ml) were higher than those from patients with a low viral load (< 400 copies/ml), only the increase in IL-1 beta level associated with deep pockets was significant (P < 0.05). There was also a trend of an increase in all the three cytokines among intravenous drug-abusing HIV-1-infected patients in comparison to non-intravenous drug abusers, but only the difference in IL-1 beta levels from deep pockets reached significance (P < 0.05). These enhanced pro-inflammatory cytokine levels in the gingival crevicular fluid of HIV-positive patients may be an important factor in causing the advanced periodontal lesions sometimes observed in HIV-positive patients.
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PMID:Enhanced interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in gingival crevicular fluid from periodontal pockets of patients infected with human immunodeficiency virus 1. 1115 68

Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry extract. They are natural remedies with antiviral properties, especially against different strains of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody level to influenza virus in the Sambucol group, than in the control group. The present study aimed to assess the effect of Sambucol products on the healthy immune system - namely, its effect on cytokine production. The production of inflammatory cytokines was tested using blood - derived monocytes from 12 healthy human donors. Adherent monocytes were separated from PBL and incubated with different Sambucol preparations i.e., Sambucol Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45 fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. Sambucol could also have an immunoprotective or immunostimulatory effect when administered to cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view of the increasing popularity of botanical supplements, such studies and investigations in vitro, in vivo and in clinical trials need to be developed.
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PMID:The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. 1139 18

All-trans-retinoic acid (RA) has been shown either to activate or repress human immunodeficiency virus type 1 (HIV-1) replication in primary monocyte-derived-macrophages (MDMs). We systematically investigated the contribution that cell donor and virus differences make to this variability. We found that the effect of RA was cell donor dependent. In addition, the ability of RA to repress HIV-1 replication varied between different virus stocks. In no case did RA affect either virus entry or integration but instead affected the accumulation of viral mRNAs in infected cells. Despite the complex variability in RA responsiveness in untreated cells, we found that RA consistently repressed virus replication when the MDMs were treated with concentrations of interleukin 1 beta (IL-1 beta) and IL-6 that are expected at local sites of infection, where HIV-1-infected macrophages reside in vivo.
AIDS Res Hum Retroviruses 2002 Jun 10
PMID:Interleukin 1 beta and interleukin 6 potentiate retinoic acid-mediated repression of human immunodeficiency virus type 1 replication in macrophages. 1207 60

During pregnancy, a complex cytokine network is present at the maternal-fetal interface in order to support normal growth and development of the placenta and fetus. HIV can frequently infect placental trophoblast but the impact of cytokines produced locally by the placenta and decidua on virus expression and replication is unknown. We comprehensively assayed the cytokines typically present in the placental microenvironment for their potential to modulate HIV transcriptional activation in the isolated trophoblast cells employing a transient transfection assay with luciferase as a reporter gene. Long terminal repeats (LTRs) of two divergent virus strains, HIV-1 LAI and HIV-1 NDK, were used to analyze virus-specific features. Four cytokines, epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha), were found to stimulate promoters of both viruses, whereas interferon alpha (IFN-alpha) and IFN-beta were found to suppress the transcription driven from both promoters. The differences observed between the two viruses did not reach a statistically significant level. None of the remaining cytokines, including EGF; GM-CSF; insulin-like growth factor I (IGF-I); IFN-alpha, IFN-beta, and IFN-gamma; IL-1 alpha, IL-1 beta, IL-2, IL-6, and IL-10; leukemia inhibitory factor (LIF); macrophage colony-stimulating factor (M-CSF); platelet-derived growth factor BB (PDGF-BB); transforming growth factor beta (TGF-beta); and TNF-alpha, affected transcriptional expression of the promoter constructs. Our results demonstrate that the local balance of cytokines may be critical for activation of HIV in the syncytiotrophoblast-cytotrophoblast layer and thus play an important role in the transmission of virus across the placental barrier.
AIDS Res Hum Retroviruses 2002 Aug 10
PMID:Role of placental cytokines in transcriptional modulation of HIV type 1 in the isolated villous trophoblast. 1220 6

Sulphonamides, such as sulphamethoxazole (SMX) and the related sulphone dapsone (DDS), show a higher incidence of cutaneous drug reactions (CDRs) in patients with the acquired immunodeficiency syndrome (AIDS) compared with human immunodeficiency virus (HIV) negative patients. During HIV infection, pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are increased. We hypothesized that this increase in pro-inflammatory cytokines may increase the toxicity of the arylhydroxylamine metabolites of SMX (S-NOH) and DDS (D-NOH) in keratinocytes through a reduction in glutathione (GSH) content. We evaluated the effect of TNF-alpha on GSH levels in normal human epidermal keratinocytes (NHEK) and found a significant decrease in GSH after 24h. Pre-treatment with TNF-alpha also resulted in an increase in the recovery of D-NOH, but failed to alter drug-protein covalent adduct formation in NHEK. We also evaluated the effect of TNF-alpha, IL-1 beta, interferon-gamma (IFN-gamma), lipopolysaccharide (LPS) and conditioned media (obtained from monocytes stimulated with LPS) on the cytotoxicity of pre-formed arylhydroxylamine metabolites in NHEK. Priming cells with cytokines did not significantly alter the cytotoxicity of the metabolites. The effect of pre-treatment with TNF-alpha on reactive oxygen species (ROS) generation in NHEK was also determined. While ROS formation in NHEK was increased in the presence of D-NOH, TNF-alpha did not alter the level of ROS generation. Our data suggest that the level of GSH reduction induced by pro-inflammatory cytokines does not predispose NHEK to cellular toxicity from either S-NOH or D-NOH.
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PMID:Effect of pro-inflammatory cytokines on the toxicity of the arylhydroxylamine metabolites of sulphamethoxazole and dapsone in normal human keratinocytes. 1628 51

A genotype in the IL-1 gene cluster is associated with an increased risk of periodontitis. We investigated whether polymorphisms in the IL-1A +4845 and IL-1B +3954 loci affect the periodontal status of HIV-infected Brazilians on HAART. HIV-positive and HIV-negative subjects with periodontitis were genotyped for IL-1 by polymerase chain reaction and restriction enzyme digestion. Only 11.4% of patients were genotype positive. No associations between genotype positivity and HIV infection or periodontal status were found in this population.
AIDS 2006 Aug 22
PMID:IL-1 gene polymorphism and periodontal status of HIV Brazilians on highly active antiretroviral therapy. 1693 44

The interaction of HIV-1 with Toll-like receptors (TLR) on host target cells is incompletely understood. Data from several in vivo and in vitro model systems suggest that TLR2, TLR4, and TLR9 remain functional and if stimulated, cause an upregulation of viral replication. In the present studies employing two different chronically HIV-1-infected cell lines and highly purified TLR agonists, we found ligation of TLR2 and TLR9, but not TLR4, resulted in significant upregulation of HIV-1 production. This result was not due to a lack of TLR4 expression or impaired NF-kappa B activation. Using HEK293 cells transfected with individual TLRs and an HIV-1 LTR reporter confirmed that TLR4 signaling does not directly activate the HIV-1 LTR. Finally, ultrapurified LPS did not enhance production of IL-1 beta or IL-6 in chronically infected U1 cells, whereas significant cytokine production was observed in uninfected U937 cells. These results confirm the biological activity of ultrapurified LPS and raise the possibility that TLR4 signaling pathways may be altered during chronic HIV-1 infection. Collectively, these studies suggest that although several TLR can upregulate NF-kappaB in HIV-1-infected cells, upregulation of NF-kappaB alone is insufficient to activate the viral LTR. Further dissection of the TLR signaling pathways is necessary to determine how TLR stimulation leads to LTR activation and whether HIV-1 infection can alter signaling through TLR4.
AIDS Res Hum Retroviruses 2007 Nov
PMID:Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation. 1818 82


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