Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication

Cinque, Paola; Vago, Luca; Mengozzi, Manuela; Torri, Valter; Ceresa, Daniela; Vicenzi, Elisa; Transidico, Pietro; Vagani, Ambrogio; Sozzani, Silvano; Mantovani, Alberto; Lazzarin, Adriano; Poli, Guido

doi:10.1097/00002030-199811000-00014

Cited by 237 publications

(169 citation statements)

References 21 publications

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“…The secretion of both chemokines is up-regulated after in vitro HIV infection of primary PBMCs and MDM (56,81) or after IL-6 stimulation of MDM and promonocytic U1 and U937 cells (15). In vivo, increased levels of CXCL8/IL-8 were observed in the lymphoid tissues of HIV ϩ individuals (16), whereas high levels of CCL2/MCP-1 were observed in the cerebrospinal fluid of AIDS patients with either CMV-or HIV-associated encephalitis (58,82). Both chemokines were shown to up-regulate HIV replication in primary PBMC and MDM infected in vitro (16,57) as Only the E-86 plasmid showed superior baseline levels as well as responsiveness to IL-6 and inhibition by PTX-B.…”

Section: Discussionmentioning

confidence: 99%

“…7A). To correlate this strong inhibitory effect to that of other cellular genes, we investigated PTX-B's capacity to interfere with chemokines such as CXCL8/IL-8 and CCL2/MCP-1, which are transcriptionally regulated by AP-1 (53,54) and can up-regulate HIV replication both in vitro (16,(55)(56)(57) and in vivo (58). Neither chemokine was detectable in the culture supernatants of either unstimulated or PTX-B-stimulated U1 (data not shown) and U1-CR1 (Fig.…”

Section: Ptx-b Prevents Hiv Production and Cxcl8/il-8 And Ccl2/ Mcp-1mentioning

confidence: 99%

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Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

Rizzi

Crippa²,

Jeeninga

et al. 2006

The Journal of Immunology

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Pertussis toxin B-oligomer (PTX-B) inhibits HIV replication in T lymphocytes and monocyte-derived macrophages by interfering with multiple steps of the HIV life cycle. PTX-B prevents CCR5-dependent (R5) virus entry in a noncompetitive manner, and it also exerts suppressive effects on both R5- and CXCR4-dependent HIV expression at a less-characterized postentry level. We demonstrate in this study that PTX-B profoundly inhibits HIV expression in chronically infected promonocytic U1 cells stimulated with several cytokines and, particularly, the IL-6-mediated effect, a cytokine that triggers viral production in these cells independently of NF-κB activation. From U1 cells we have subcloned a cell line, named U1-CR1, with increased responsiveness to IL-6. In these cells, PTX-B neither down-regulated the IL-6R nor prevented IL-6 induced signaling in terms of STAT3 phosphorylation and DNA binding. In contrast, PTX-B inhibited AP-1 binding to target DNA and modified its composition with a proportional increases in FosB, Fra2, and ATF2. PTX-B inhibited IL-6-induced HIV-1 long-terminal repeat-driven transcription from A, C, E, and F viral subtypes, which contain functional AP-1 binding sites, but failed to inhibit transcription from subtypes B and D LTR devoid of these sites. In addition, PTX-B inhibited the secretion of IL-6-induced, AP-1-dependent genes, including urokinase-type plasminogen activator, CXCL8/IL-8, and CCL2/monocyte chemotactic protein-1. Thus, PTX-B suppression of IL-6 induced expression of HIV and cellular genes in chronically infected promonocytic cells is strongly correlated to inhibition of AP-1.

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Section: Discussionmentioning

confidence: 99%

Section: Ptx-b Prevents Hiv Production and Cxcl8/il-8 And Ccl2/ Mcp-1mentioning

confidence: 99%

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

Rizzi

Crippa²,

Jeeninga

et al. 2006

The Journal of Immunology

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“…In humans and other vertebrate animals, activated T cells that infiltrate the CNS during encephalitic DNA or RNA viral infections up-regulate expression of the chemokine receptors CCR1, CCR2, CCR5, and CXCR3 and their chemokine ligands CCL2 (CCR2), CCL3 (CCR1, CCR5), CCL4 (CCR5), CCL5 (CCR1, CCR5), and CXCL9 -CXCL11 (CXCR3) (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Although targeted deletion of CXCR3 or CXCL10 is associated with a reduction in infiltrating mononuclear cells and enhanced mortality from infection of the CNS with mouse hepatitis virus (MHV) 3 (25,26), few studies have examined regional differences in the expression of chemokine ligands during viral encephalitis.…”

Section: T He Infiltration Of Virus-specific Cd8 T Cells Is Essentialmentioning

confidence: 99%

CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

Zhang

Chan

Liu

et al. 2008

The Journal of Immunology

164

147

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Regional differences in inflammation during viral infections of the CNS suggest viruses differentially induce patterns of chemoattractant expression, depending on their cellular targets. Previous studies have shown that expression of the chemokine CXCL10 by West Nile virus (WNV)-infected neurons is essential for the recruitment of CD8 T cells for the purpose of viral clearance within the CNS. In the current study we used mice deficient for the CXCL10 receptor, CXCR3, to evaluate its role in leukocyte-mediated viral clearance of WNV infection within various CNS compartments. WNV-infected CXCR3-deficient mice exhibited significantly enhanced mortality compared with wild-type controls. Immunologic and virologic analyses revealed that CXCR3 was dispensable for control of viral infection in the periphery and in most CNS compartments but, surprisingly, was required for CD8 T cell-mediated antiviral responses specifically within the cerebellum. WNV-specific, CXCR3-expressing T cells preferentially migrated into the cerebellum, and WNV-infected cerebellar granule cell neurons expressed higher levels of CXCL10 compared with similarly infected cortical neurons. These results indicate that WNV differentially induces CXCL10 within neuronal populations and suggest a novel model for nonredundancy in chemokine-mediated inflammation among CNS compartments.

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“…However, a significant upregulation or dysregulation of CNS expression of CCL2 occurs in a variety of acute and chronic neuroinflammatory and neurodegenerative CNS disorders, implicating a role for CCL2 in pathological conditions. For example, CCL2 levels in the CNS are elevated in brain injury (Little et al, 2006), cerebral ischemia (Che et al, 2001;Minami et al, 2006), multiple sclerosis (Mahad and Ransohoff, 2003;McManus et al, 1998), human immunodeficiency virus (HIV)-associated dementia (Cinque et al, 1998) and Alzheimer's disease (Galimberti et al, 2006). Both neurotoxic and neuroprotective roles for CCL2 have been proposed in these conditions.…”

Section: Introductionmentioning

confidence: 99%

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

Cho

Gruol

2008

Journal of Neuroimmunology

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Emerging evidence indicates that chemokines can regulate both the physiology and biochemistry of CNS neurons and glia. In the current study, Western blot analysis showed that in rat hippocampal neuronal/glial cultures the signal transduction pathway activated by CCL2, a chemokine expressed in the normal brain and at elevated levels during neuroinflammation, involves a G-protein coupled receptor, p38 MAPK as well as its immediate upstream kinase MKK3/6, and the downstream transcription factor CREB. ERK 1/2 and the transcription factors STAT1 and STAT3 do not play a prominent role. CCL2 also altered Ca 2+ influx and synaptic network activity in the hippocampal neurons. These results suggest an important role for p38 MAPK and CREB in hippocampal actions of CCL2.

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Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication

Abstract: Taken together, these in vivo and in vitro findings support a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclear cells via HIV-induced MCP-1.

Cited by 237 publications

References 21 publications

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

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