Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry

Wesselingh, Steven Lodewyk; Takahashi, Kiyomi; Glass, Jonathan D.; McArthur, Justin C.; Griffin, John W.; Griffin, Diane E.

doi:10.1016/s0165-5728(96)00160-9

Cited by 153 publications

(115 citation statements)

References 40 publications

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“…TNF-a is a proin¯ammatory cytokine with a wide variety of actions that could contribute to CNS in¯ammation including upregulation of IL-1 and IL-6 expression, activation of lymphocytes and macrophages, and increased cell adhesion molecule expression by endothelial cells (Abbas et al, 1991). TNF-a is elevated in the brains of patients with HIV dementia (Wesselingh et al, 1993) and as in OvLV is produced primarily by perivascular macrophages (Wesselingh et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Craig¹,

Sheffer²,

Meyer³

et al. 1997

J Neurovirol

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The lentiviruses of sheep replicate almost exclusively in macrophages and cause chronic interstitial pneumonia, arthritis, and mastitis, but only rarely encephalitis. This study was undertaken to determine whether a nonneurovirulent ®eld strain of ovine lentivirus isolated from joint¯uid that replicated productively in lung and joint macrophages could be adapted to enter and replicate in the brain and cause encephalitis. The ®eld isolate was passed seven times sequentially by intracerebral inoculation of sheep. The neuroadapted strain of virus caused severe encephalitis typical of visna in four of four sheep inoculated intracerebrally. The virus replicated to high titers in the brains of these animals and in cultured microglia. The in¯ammatory response in the brain was characterized by intense in®ltrates of macrophages and CD8 + and CD4 + T cells. Many of the perivascular macrophages demonstrated TNF-a expression and there was upregulation of MHC Class II antigen expression on both in¯ammatory cells and endothelium. Inoculation of this neuroadapted virus into the bone marrow of three animals resulted in persistent infection and cell-associated viremia, but not encephalitis. Virus was not detected in brains from these animals, indicating that the virus was not neuroinvasive. These data suggest that neuroinvasiveness and neurovirulence are separate pathogenic determinants, both of which are required for the development of encephalitis during natural infection.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Craig¹,

Sheffer²,

Meyer³

et al. 1997

J Neurovirol

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“…44,45 In contrast, increased numbers of microglia, 44 elevated TNF-a mRNA in microglia and astrocytes, 46 evidence of excitotoxins, [47][48][49] decreased synaptic and dendritic density, 45,50 and selective neuronal loss 51,52 constitute the pathologic features most closely associated with the clinical signs of HAD. Furthermore, signs of neuronal apoptosis have been linked to HAD, [53][54][55] although this finding is not clearly associated with viral burden 53 or a history of dementia.…”

Section: Potential Links Between Neuropathology Of Hiv Infection and mentioning

confidence: 99%

“…81,125 In addition to chemokines and EAAs, HIV-infected or gp120-activated microglia also release inflammatory cytokines, including TNF-a and IL-1b. 46,132 Among other actions, both of these cytokines stimulate release of L-cysteine from macrophages, and pharmacologic blockade of IL-1b or antibody neutralization of TNF-a prevents this release. 60 Under physiological or pathophysiological conditions, Lcysteine can stimulate NMDARs and lead to neuronal apoptosis.…”

Section: Mechanisms Of Neuronal Injury and Death In Hadmentioning

confidence: 99%

“…Expression of TNF-a and its receptor are elevated in brains from patients with HAD. 46 Experiments aimed at addressing the question of interactions between neurotoxins associated with HAD have revealed that TNF-a and HIV/Tat synergize to promote neuronal death, and this effect is prevented by antioxidants. 135 It remains possible that TNF-a can activate caspases within neurons via TNF-a receptor-1 (TNFR1), since TNFR1 is found on at least some neurons, and it can trigger caspase-8 activation.…”

Section: Mechanisms Of Neuronal Injury and Death In Hadmentioning

confidence: 99%

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HIV-1 infection and AIDS: consequences for the central nervous system

et al. 2005

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Infection with the human immunodeficiency virus-1 (HIV-1) can induce severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia. After infiltrating peripheral immune competent cells, in particular macrophages, HIV-1 provokes a neuropathological response involving all cell types in the brain. HIV-1 also incites activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can trigger numerous downstream signaling pathways and disrupt neuronal and glial function. This review will discuss recently uncovered pathologic neuroimmune and degenerative mechanisms contributing to neuronal damage induced by HIV-1 and potential approaches for development of future therapeutic intervention.

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“…IL-1␤ is up-regulated in vivo in both cerebral spinal fluid and brain of HAD patients (10 -12), and macrophage/ microglia is the primary cell type in CNS responsible for its production (7,13). Exposure of macrophages to whole HIV-1 virions or envelope (Env) glycoprotein gp120 has been shown in many in vitro systems to induce IL-1␤ release independently of productive infection (14,15).…”

mentioning

confidence: 99%

Signaling Mechanism of HIV-1 gp120 and Virion-Induced IL-1β Release in Primary Human Macrophages

Cheung

Ravyn

Wang

et al. 2008

The Journal of Immunology

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HIV-1 envelope glycoprotein gp120 induces, independently of infection, the release of proinflammatory cytokines, including IL-1β from macrophages, that are implicated in the pathogenesis of HIV-associated dementia. However, the signal transduction pathways involved have not been fully defined. Previously, our laboratory reported that soluble gp120 activates multiple protein kinases in primary human monocyte-derived macrophages, including the Src family kinase Lyn, PI3K, and the focal adhesion-related proline-rich tyrosine kinase Pyk2. In this study we showed that gp120 induces IL-1β release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to Giα protein. Using pharmacological inhibitors and small interfering RNA gene knockdown, we demonstrated that concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1β production. By coimmunoprecipitation and immunofluorescence confocal microscopy, we showed that CCR5 activation by gp120 triggered the assembly of a signaling complex involving endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn. Finally, we demonstrated that virion-associated gp120 induced similar response, as structurally intact whole virions also triggered IL-1β release and re-localization of PI3K and Pyk2. This study identifies a novel signaling mechanism for HIV-1-induced IL-1β production by primary human macrophages that may be involved in the neuropathogenesis of HIV-associated dementia.

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Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry

Cited by 153 publications

References 40 publications

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

HIV-1 infection and AIDS: consequences for the central nervous system

Signaling Mechanism of HIV-1 gp120 and Virion-Induced IL-1β Release in Primary Human Macrophages

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