Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1.

Wahl, Larry M.; Corcoran, Marta L.; Pyle, Stephen W.; Arthur, Larry O.; Harel‐Bellan, Annick; Farrar, William L.

doi:10.1073/pnas.86.2.621

Cited by 241 publications

(149 citation statements)

References 36 publications

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“…The finding that peak cysteine levels occurred 96 h after gp120 application but only 24 h after cytokine application was consistent with the hypothesis that gp120 must first cause the elaboration of cytokines, a known event (26), to induce cysteine release. To test this hypothesis, we pretreated macrophages with TNF-neutralizing Ab (␣TNF), IL-1 receptor antagonist (IRA), or both.…”

Section: Gp120-induced Cysteine Release Is Partially Inhibited By Tnfsupporting

confidence: 86%

“…Furthermore, peak cysteine levels occurred earlier after cytokine stimulation than with gp120 stimulation, consistent with the notion that gp120 may act by first inducing cytokine secretion. In fact, previous studies have shown that gp120 stimulates the secretion of both TNF-␣ and IL-1␤ by human monocytic cells (26,27). As alluded to previously, TNF-␣ and IL-1␤ are elevated in the brain, spinal cord, and cerebrospinal fluid of AIDS patients (47,48).…”

Section: Discussionmentioning

confidence: 98%

“…First, gp120 can cause the elaboration of cytokines from human macrophages and rat microglia, including TNF-␣ and IL-1␤ (26,27). Second, a study by Gmünder et al (28) reported that mouse peritoneal macrophages stimulated with TNF-␣ release cysteine.…”

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confidence: 99%

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Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine

Yeh

Kaul

Zheng

et al. 2000

The Journal of Immunology

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Approximately one-quarter of individuals with AIDS develop neuropathological symptoms that are attributable to infection of the brain with HIV. The cognitive manifestations have been termed HIV-associated dementia. The mechanisms underlying HIV-associated neuronal injury are incompletely understood, but various studies have confirmed the release of neurotoxins by macrophages/microglia infected with HIV-1 or stimulated by viral proteins, including the envelope glycoprotein gp120. In the present study, we investigated the possibility that l-cysteine, a neurotoxin acting at the N-methyl-d-aspartate subtype of glutamate receptor, could contribute to HIV-associated neuronal injury. Picomolar concentrations of gp120 were found to stimulate cysteine release from human monocyte-derived macrophages (hMDM) in amounts sufficient to injure cultured rat cerebrocortical neurons. TNF-α and IL-1β, known to be increased in HIV-encephalitic brains, as well as a cellular product of cytokine stimulation, ceramide, were also shown to induce release of cysteine from hMDM in a dose-dependent manner. A TNF-α-neutralizing Ab and an IL-1βR antagonist partially blocked gp120-induced cysteine release, suggesting that these cytokines may mediate the actions of gp120. Interestingly, hMDM infected with HIV-1 produced significantly less cysteine than uninfected cells following stimulation with TNF-α. Our findings imply that cysteine may play a role in the pathogenesis of neuronal injury in HIV-associated dementia due to its release from immune-activated macrophages but not virus-infected macrophages. Such uninfected cells comprise the vast majority of mononuclear phagocytes (macrophages and microglia) found in HIV-encephalitic brains.

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Section: Gp120-induced Cysteine Release Is Partially Inhibited By Tnfsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 98%

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Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine

Yeh

Kaul

Zheng

et al. 2000

The Journal of Immunology

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“…Several factors play a key role in immunedysregulation. During acute infection, levels of proinflammatory cytokines are upregulated systemically, largely consisting of IL-6, IL-1β, and TNF-α, consequently induced by HIV-1 surface glycoproteins in in vitro cultured PBMC [79][80][81] and in vivo [82], or associated with viral replication [83]. Similarly, HIV infection and several HIV-specific gene products are responsible for T-cell activation.…”

Section: Relative Levels Of Foxp3 and Treg During Hiv-1 Infection Andmentioning

confidence: 99%

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

et al. 2008

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FoxP3 + CD4 + CD25 + regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed. KeywordsRegulatory T cells; AIDS; Chromatin; Epigenetic; Humanized mouse; DKO-hu; ONTAK Regulatory T cells play an important role in self immune tolerance and in balanced immune responsesThe regulation of immune tolerance is a critical aspect of immunology. The balance between recognition of self versus non-self is essential for maintenance of immune homeostasis. Regulatory T cells (CD4 + CD25 + ) are a crucial component for the control of deleterious effects from excessive immune responses as seen in autoimmune disease or allergic insult [1,2]. Treg cells have been implicated in a number of pathologic processes including elevated levels in cancers [3][4][5] and infectious diseases [6][7][8][9], and reduced levels in autoimmune diseases [1,[10][11][12][13]. It is apparent that Treg cells are induced (or recruited and expanded) by most infections to modulate host immune responses to avoid overreactive immunity (Fig. 1). As a result, Treg play a critical role in immune responses, vaccinations as well as in immunopathogenesis of pathogens. For example, Leishmania infection leads to induction of Treg that help to maintain the balance of immune response and pathogen persistence [18,19]. For the host, persistence of the pathogen is beneficial to maintain effective immunity against these pathogens [18]. In a number of chronic viral infections, Treg are induced to subdue the anti-viral immune responses and allow persistent infection. Mechanisms of CD4 T-cell differentiationT-cell lineage commitment and activation of T cells are usually accompanied by changes in patterns of gene expression. During T-cell responses, T helper (Th) progenitor cells will undergo Th1 or Th2 lineage commitments involving well-defined initiation cytokines, transcription factors, and effector cytokines. Expression of T-bet and GATA3 in Th1 and Th2 cells, respectively, is epigenetically regulated by histone modification and DNA methylation. As T lineage determinants, T-bet or GATA3 are also involved in epigenetically reprogramming the T-cell genome to silence the Th2 or Th1 effector cytokines, respectively, and to activate Th1 or Th2 cytokine genes for transcription (Fig. 2). Similarly, Th17 cell differentiation requires IL-6/TGF-β (mo...

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“…In vitro production of PGE 2 and thromboxane B 2 by PBM from AIDS patients is increased relative to normal controls (11,12). Experimental infection of human PBM with HIV-1 also results in increased production of PGE 2 relative to uninfected control cultures (13)(14)(15)(16). PG can be converted non-enzymatically to other compounds, including cyclopentenone PG (cyPG) (17).…”

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confidence: 99%

Peroxisome Proliferator-activated Receptor γ Agonists Inhibit HIV-1 Replication in Macrophages by Transcriptional and Post-transcriptional Effects

Hayes¹,

Lane²,

King³

et al. 2002

Journal of Biological Chemistry

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Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1.

Cited by 241 publications

References 36 publications

Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine

Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

Peroxisome Proliferator-activated Receptor γ Agonists Inhibit HIV-1 Replication in Macrophages by Transcriptional and Post-transcriptional Effects

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