Microglial Activation and Neurological Symptoms in the SIV Model of NeuroAIDS: Association of MHC-II and MMP-9 Expression with Behavioral Deficits and Evoked Potential Changes

Berman, Nancy E.J.; Marcario, Joanne K.; Yong, Chi; Raghavan, Ravi; Raymond, Leigh A.M.; Joag, Sanjay V.; Narayan, Opendra; Cheney, Paul D.

doi:10.1006/nbdi.1999.0261

Cited by 58 publications

(33 citation statements)

References 59 publications

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“…In contrast, low progressors exhibit low levels of MMP-9, similar to uninfected controls. 29 In addition, in vitro studies reported that HIV or the HIV Tat protein could promote MMP-9 secretion from monocytes, 32 whereas MMP-2 secretion could be stimulated by gp41-derived peptides. 27 Because chemokine receptors are expressed in normal brain and in brain from AIDS patients, 58 our results raise the hypothesis that secretion of MMP-9 in the CNS could not only be induced by MIP-1␣ (CCL3) and MIP-1␤, and, to a lesser extent, RANTES (CCL5), 59 but could also be up-regulated by gp120 through the CXCR4 or CCR5 coreceptors independently of CD4.…”

Section: Discussionmentioning

confidence: 99%

“…Because MMP-9 has been associated with a number of neurodegenerative processes, including demyelinization, 40 and has also been found in the cerebrospinal fluid of patients with AIDS, 29 we investigated whether binding of gp120 could induce the production of MMP-9 by C6 glioma cells and T cells. Our results show that stimulation with either gp120 or chemokines significantly upregulated the secretion of MMP-9 by both glioma cells ( Figure 5) and T cells (Figure 6), as detected by gelatin zymography.…”

Section: Gp120 From Hiv-1 Hxb2 or Jrfl And Sdf-1␣ Or Mip-1␤ Induce MMmentioning

confidence: 99%

“…26,28 In rapidly progressing simian immunodeficiency virus-infected monkeys, high expression of MMP-9 was correlated to both motor and cognitive deficits; in contrast, low progressors exhibited low levels of MMP-9, similar to uninfected control. 29 In addition, in vitro studies reported evidence that HIV itself, or at least the HIV Tat or Nef proteins directly promote MMP-9 secretion. [30][31][32] The principal aim of this study was to assess the importance of coreceptors, in some pathogenic pathways induced by their respective chemokine or gp120 ligands, without the participation of the CD4 receptor.…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Missé

Estève

Renneboog

et al. 2001

Blood

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It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp120) activates cell signaling by CXCR4, independently of CD4. The present study examines the involvement of different intracellular signaling pathways and their physiopathologic consequences following the CD4-independent interaction between CXCR4 or CCR5 and gp120 in different cell types: primary T cells, CD4 ؊ / CXCR4 ؉ /CCR5 ؉ T cells, or glioma cells. These interactions were compared with those obtained with natural ligands, stromal cell-derived factor 1 ␣ (SDF-1␣) (CXCL12) and macrophage inflammatory IntroductionAIDS results from different actions induced by HIV on its wide variety of target cells. The CD4 molecule is the major receptor of HIV-1. 1 The high-affinity binding of CD4 to glycoprotein 120 (gp120) 2 induces conformational changes in gp120 to allow its further binding to secondary receptors, 3-5 which could result in a trimolecular complex, CD4-gp120-coreceptor. 6,7 HIV coreceptors belong to the chemokine receptor family (see Baggiolini et al 8 for review), among which CXCR4 and CCR5 are the major attachment coreceptors for T-tropic and M-tropic isolates of HIV-1, respectively. 9,10 The HIV envelope binding to target cells induces activation through receptors, 11,12 eliciting functional responses that are important in AIDS pathogenesis. Although the cell activation is induced by a CD4-transconformed gp120 through the coreceptor, 13-15 a CD4-independent activation occurs, 16,17 particularly in T cells and cells from the central nervous system (CNS). 18,19 Indeed, it has been reported that cell signaling is activated by either the X4-tropic or R5-tropic HIV-1 envelopes, leading to activation of such functional responses as proliferation, differentiation, chemotaxis, 13,16 proinflammatory cytokines secretion, or apoptosis. 20,21 Apoptosis or programmed cell death is one of the major physiopathologic mechanisms of AIDS. Cells continuously stimulated become sensitive to apoptosis. 22 Interactions between 23 or between tumor necrosis factor ␣ (TNF␣) and its receptor (TNFr), activation of caspases, and down-regulation of the proto-oncogene Bcl2 protein and interleukin-2 (IL2) are considered the major apoptotic events during HIV infection leading to destruction of T cells, 24 macrophages, dendritic cells, and neurons.In the CNS, another important factor contributing to the neurodegenerative process is the presence of extracellular proteases from the matrix metalloproteinase (MMP) family. MMPs have been shown to degrade constituents of the extracellular matrix such as collagens, 25 favoring (1) The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734. For personal use only. on April 4, 2019. by guest www.bloodjournal.org From destruction of the extracellular matrix in vivo or in vitro. 27 The presence of MMP-9 was reported in cerebrospinal fluid of HIVinfected patients. 26,2...

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Section: Discussionmentioning

confidence: 99%

Section: Gp120 From Hiv-1 Hxb2 or Jrfl And Sdf-1␣ Or Mip-1␤ Induce MMmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Missé

Estève

Renneboog

et al. 2001

Blood

View full text Add to dashboard Cite

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“…[11][12][13][14] Tissue inhibitors of metalloproteinases (TIMPs) are a family of proteinase inhibitors that control the activity of MMPs in vivo by binding in 1:1 stoichiometry. 15,16 Disruption of this balance is seen in various pathological conditions such as neuroAIDS, 17 Alzheimer's disease, 18 multiple sclerosis, 19 brain tumors, 20 epilepsy, 21 and excitotoxic/ neuroinflammatory processes. 22 In the case of HIV infection, once the HIV enters into the CNS, it leads to neuronal damage, which in turn causes cognitive issues (eg, attention, memory, language, problem solving, and decision-making), and eventually leads to the HAND.…”

Section: Introductionmentioning

confidence: 99%

Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Atluri¹,

Jayant²,

Pilakka-Kanthikeel³

et al. 2016

IJN

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Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients.

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“…Upregulation of MMPs has been reported in multiple sclerosis, stroke, HIV-dementia, bacterial meningitis, Alzheimer's disease and brain tumors [43,46,47,63]. Animal models used to study distinct CNS disorders have concentrated on the use of MMP inhibitors or MMP deficient animals to evaluate the lack of MMPs in the progression of the disorder [7,24,28,29,35,43]. Studies in humans have focused on detection of MMPs in serum, CSF or post-mortem specimens, and in general the data obtained correlates positively with the severity of the disorder [5,14,22,26,33,48].…”

Section: Introductionmentioning

confidence: 99%

Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers

Alvarez

Teale

2008

Brain Research

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During the course of murine neurocysticercosis (NCC), disruption of the unique protective barriers in the central nervous system (CNS) is evidenced by extravasation of leukocytes. This process varies according to the anatomical sites and diverse vascular beds analyzed. To examine mechanisms involved in the observed differences, the expression and activity of eight matrix metalloproteinases (MMPs) were analyzed in a murine model of NCC. The mRNA expression of the MMPs studied was upregulated as a result of infection, and active MMPs were mainly detected in leukocytes migrating into the brain. Polarized expression and gelatinolytic activity of several MMPs were identified in immune cells extravasating pial vessels as early as 1 day post infection. In contrast, leukocytes expressing active MMPs and extravasating parenchymal vessels were not observed until 5 weeks post infection. In ventricular areas, most of the MMP activity was detected in leukocytes traversing the ependyma from leptomeningeal infiltrates. In addition, immune cells continued to express active MMPs after exiting vessels suggesting that enzymatic activity of MMPs is not just required for diapedesis. These results correlate with our previous studies showing differential kinetics in the disruption of the CNS barriers upon infection and help document the important role of MMPs during leukocyte infiltration and inflammation.

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Microglial Activation and Neurological Symptoms in the SIV Model of NeuroAIDS: Association of MHC-II and MMP-9 Expression with Behavioral Deficits and Evoked Potential Changes

Cited by 58 publications

References 59 publications

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers

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