HIV-1 tat protein induces the production of interleukin-8 by human brain-derived endothelial cells

Hofman, Florence M.; Chen, Pei-Jia; Incardona, Francesca; Zidovetzki, Raphael; Hinton, David R.

doi:10.1016/s0165-5728(98)00198-2

Cited by 80 publications

(59 citation statements)

References 60 publications

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“…As mentioned before, Tat induces the expression of E-selectin, up-regulates ICAM-1 and VCAM-1 in macrovascular and microvascular EC [69,70,112,113] and supports leukocyte adhesion. Furthermore, it stimulates transcription and release of IL-8 [112] and MCP-1 [93] that are powerful leukocytes chemoattractants. In vivo, the effect of Tat on leukocyte recruitment is preceded by an increased in vascular permeability, which is caused by the synthesis of platelet-activating factor in EC and may facilitate cell transmigration [93].…”

Section: Regulation Of Leukocytes Diapedesis By Ecmentioning

confidence: 60%

Interactions between endothelial cells and HIV-1

Bussolino

Mitola

Serini

et al. 2001

The International Journal of Biochemistry &Amp; Cell Biology

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Endothelial cells (EC) participate in inflammatory and immune reactions by producing and responding to soluble mediators. Human immunodeficiency virus (HIV)-1 profoundly alters the features of EC. In some anatomical districts, they are infected by the virus and may represent a relevant reservoir. During lymphomononuclear cell diapedesis, EC activate virus replication in crossing cells. Direct or indirect damage of EC is particularly relevant in central nervous system, where blood-brain barrier perturbation is pivotal in neuronal degeneration. The observed alterations of EC adhesive properties contribute in altered leukocyte traffic from blood to lymphoid organs and tissues and play a role in the onset of immune surveillance alteration. These alterations of EC functions are relevant for the general vasculopathy, which marks the acquired immunodeficiency syndrome, and in particular are instrumental in the pathogenesis of Kaposi's sarcoma. Here we discuss the biological and molecular activation of EC in HIV-1 infection that represents the basis to understand the pathogenesis of HIV-1 associated vascular diseases.

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Section: Regulation Of Leukocytes Diapedesis By Ecmentioning

confidence: 60%

Interactions between endothelial cells and HIV-1

Bussolino

Mitola

Serini

et al. 2001

The International Journal of Biochemistry &Amp; Cell Biology

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“…In addition, HIV-1 Tat protein induced the production of IL-8 by human brain-derived EC (33,46), and increased endothelial permeability through tyrosine kinase-and mitogen-activated protein kinase-dependent pathways (34,47).…”

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confidence: 99%

HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells

Kim

Avraham

Koh

et al. 2003

The Journal of Immunology

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The integrity of the blood-brain barrier (BBB) is critical for normal brain function. Neuropathological abnormalities in AIDS patients have been associated with perivascular HIV-infected macrophages, gliosis, and abnormalities in the permeability of the BBB. The processes by which HIV causes these pathological conditions are not well understood. To characterize the mechanism by which HIV-1 Tat protein modulates human brain microvascular endothelial cell (HBMEC) functions, we studied the effects of HIV-1 Tat in modulating HBMEC apoptosis and permeability. Treatment of HBMEC with HIV-1 Tat led to Flk-1/KDR and Flt-4 receptor activation and the release of NO. The protein levels of endothelial NO synthase (NOS) and inducible NOS were increased by HIV-1 Tat stimulation. Importantly, HIV-1 Tat caused apoptosis of HBMEC, as evidenced by changes in the cleavage of poly(A)DP-ribose polymerase, DNA laddering, and incorporation of fluorescein into the nicked chromosomal DNA (TUNEL assay). HIV-1 Tat-mediated apoptosis in HBMEC was significantly inhibited in the presence of N-nitro-l-arginine methyl ester (an inhibitor of NOS) and wortmannin (a phosphoinositol 3-kinase inhibitor). Furthermore, HIV-1 Tat treatment significantly increased HBMEC permeability, and pretreatment with both N-nitro-l-arginine methyl ester and wortmannin inhibited the Tat-induced permeability. Taken together, these results indicate that dysregulated production of NO by HIV-1 Tat plays a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB.

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“…IL-8 was one of the first chemokines to be characterized and today Ͼ30 human chemokines have been described (5,6). HIV-1-infected patients express elevated levels of IL-8 that may responsible for some clinical manifestations of AIDS (7). Studies by Benfield et al (8) indicate that HIV-positive patients infected with Pneumocystis carinii express higher levels of IL-8 in bronchoalveolar lavage fluid as compared with HIV-negative individuals infected with P. carinii.…”

mentioning

confidence: 99%

“…Studies by Benfield et al (8) indicate that HIV-positive patients infected with Pneumocystis carinii express higher levels of IL-8 in bronchoalveolar lavage fluid as compared with HIV-negative individuals infected with P. carinii. HIV-derived viral proteins activate endothelial cells in the CNS to produce IL-8, which acts as a stimulator and chemoattractant for neutrophils and lymphocytes (7). However, there is limited information on the participation of chemokines in inflammatory processes within the CNS.…”

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confidence: 99%

Morphine Regulates Gene Expression of α- and β-Chemokines and Their Receptors on Astroglial Cells Via the Opioid μ Receptor

Mahajan¹,

Schwartz²,

Shanahan

et al. 2002

The Journal of Immunology

101

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The brain is a target organ for recreational drugs and HIV-1. Epidemiological data demonstrate that opioid abuse is a risk factor for HIV-1 infection and progression to AIDS. Chemokines and their receptors have been implicated in the neuropathogenesis of HIV-1 infections. However, little is known about the effects of opioids on the expression of chemokines and their receptors (the latter also are HIV-1 coreceptors) by cells of the CNS. Herein we describe the effects of morphine on gene expression of the α- and β-chemokines and their receptors by the astrocytoma cell line U87 and by primary normal human astrocyte (NHA) cultures. U87 cells treated with morphine showed significant down-regulation of IL-8 gene expression, whereas expression of the IL-8 receptor CXCR2 was reciprocally up-regulated as detected by RT-PCR. Treatment of NHAs with morphine suppressed IL-8 and macrophage-inflammatory protein-1β gene expression, whereas expression of their receptor genes, CCR3 and CCR5, was simultaneously enhanced. These morphine-induced effects on U87 and NHA cells were reversed by the opioid μ receptor antagonist β-funaltrexamine. Morphine also enhanced the constitutive expression of the opioid μ receptor on astroglial cells. Our results support the hypothesis that opioids play a significant role in the susceptibility of the CNS to HIV-1 infection and subsequent encephalopathy by inhibiting local production of HIV-1-protective chemokines (IL-8 and macrophage-inflammatory protein-1β) and enhancing expression of HIV-1 entry coreceptor genes (CCR3, CCR5, and CXCR2) within the CNS. These effects of opioids appear to be mediated through the opioid μ receptor that we demonstrated on astroglial cells.

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HIV-1 tat protein induces the production of interleukin-8 by human brain-derived endothelial cells

Cited by 80 publications

References 60 publications

Interactions between endothelial cells and HIV-1

Interactions between endothelial cells and HIV-1

HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells

Morphine Regulates Gene Expression of α- and β-Chemokines and Their Receptors on Astroglial Cells Via the Opioid μ Receptor

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