Yin and Yang of PDGF-mediated signaling pathway in the context of HIV infection and drug abuse.

The control and eradication of neurological complications associated with AIDS continues to be an important goal in efforts toward improving the well being of HIV-infected patients. Although combined antiretroviral therapies have contributed significantly to increasing the longevity of patients by suppressing the virus burden in the systemic compartments, the prevalence of HIV-associated neurological disorders continues to be on the rise. This in turn, leads to an impaired quality of life of the infected individuals who continue to suffer from mild to moderate cognitive decline and memory loss.

Platelet-derived growth factor CC-mediated neuroprotection against HIV Tat involves TRPC-mediated inactivation of GSK 3beta.

Platelet-derived growth factor-CC (PDGF-CC) is the third member of the PDGF family, and has been implicated both in embryogenesis and development of the CNS. The biological function of this isoform however, remains largely unexplored in the context of HIV-associated dementia (HAD). In the present study, we demonstrate that exposure of human neuroblastoma cells SH-SY5Y to HIV transactivator protein Tat resulted in decreased intrinsic expression of PDGF-CC as evidenced by RT-PCR and western blot assays.

Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1.

Platelet-derived growth factor (PDGF) is a pleiotropic protein with critical roles in both developmental as well as pathogenic processes. In the central nervous system specifically, PDGF is critical for neuronal proliferation and differentiation and has also been implicated as a neuroprotective agent. Whether PDGF also plays a role in synaptic plasticity, however, remains poorly understood.

Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia.

With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV-1 induces neuro-inflammation and subsequent neuronal damage is important. The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells.

PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium.

The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process.

Morphine enhances Tat-induced activation in murine microglia.

There is increasing evidence that opiates accelerate the pathogenesis and progression of acquired immunodeficiency syndrome (AIDS), as well as the incidence of human immunodeficiency virus (HIV) encephalitis (HIVE), a condition characterized by inflammation, leukocyte infiltration, and microglial activation. The mechanisms, by which the HIV-1 transactivating protein Tat and opioids exacerbate microglial activation, however, are not fully understood. In the current study, we explored the effects of morphine and HIV-1 Tat(1-72) on the activation of mouse BV-2 microglial cells and primary mouse microglia.

Involvement of TRPC channels in CCL2-mediated neuroprotection against tat toxicity.

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, plays a critical role in leukocyte recruitment and activation. In the present study, we identify an additional role for CCL2 that of neuroprotection against HIV-1 transactivator protein (Tat) toxicity in rat primary midbrain neurons. Furthermore, we report the involvement of transient receptor potential canonical (TRPC) channels in CCL2-mediated neuroprotection.

Proinflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes.

HIV encephalitis (HIVE), the pathologic correlate of HIV-associated dementia (HAD) is characterized by astrogliosis, cytokine/chemokine dysregulation, and neuronal degeneration. Increasing evidence suggests that inflammation is actively involved in the pathogenesis of HAD. In fact, the severity of HAD/HIVE correlates more closely with the presence of activated glial cells than with the presence and amount of HIV-infected cells in the brain.

Mechanisms of platelet-derived growth factor-mediated neuroprotection--implications in HIV dementia.

Platelet-derived growth factor (PDGF) has been implicated in promoting survival and proliferation of immature neurons, and even protecting neurons from gp120-induced cytotoxicity. However, the mechanisms involved in neuroprotection are not well understood. In the present study we demonstrate the role of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in PDGF-mediated neuroprotection.

Molecular mechanism(s) involved in the synergistic induction of CXCL10 by human immunodeficiency virus type 1 Tat and interferon-gamma in macrophages.

Synergistic interactions between viral proteins and soluble host factors released from infected mononuclear phagocytes play a critical role in the pathogenesis of human immunodeficiency virus (HIV)-associated dementia (HAD). The chemokine CXCL10 has been found to be closely associated with the progression of HIV-1-related central nervous system (CNS) disease and its related neuropsychiatric impairment. In this report the authors demonstrate that the HIV-1 protein Tat can interact with the proinflammatory cytokine interferon (IFN)-gamma to dramatically induce the expression of CXCL10 in macrophages.

Platelet-derived growth factor protects neurons against gp120-mediated toxicity.

The human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 has been implicated in mediating neuronal apoptosis, a hallmark feature of HIV-associated dementia (HAD). Mitigation of the toxic effects of gp120 could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study the authors hypothesized that neurotrophic factor, such as platelet-derived growth factor (PDGF), could protect the neurons against gp120-mediated apoptosis.

Cocaine-mediated enhancement of virus replication in macrophages: implications for human immunodeficiency virus-associated dementia.

Injection drug use has been recognized as a major risk factor for acquired immunodeficiency syndrome (AIDS) from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States, can both impair the functions of macrophages and CD4(+) lymphocytes and also activate human immunodeficiency virus (HIV)-1 expression in these cells. Because the brain is the target organ for both cocaine and HIV, the objective of the present study was to explore the effects of cocaine on virus replication in macrophages, the target cells for the virus in the central nervous system (CNS).

Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier: implications for HIV-dementia.

One of the hallmark features underlying the pathogenesis of HIV encephalitis is the disruption of blood-brain barrier (BBB). Cocaine, often abused by HIV-infected patients, has been suggested to worsen the HIV-associated dementia (HAD) via unknown mechanisms. The objective of the present study was to explore the effects of cocaine on BBB permeability using human brain microvascular endothelial cells (HBMECs).

Recombinant thymosin beta 4 can promote full-thickness cutaneous wound healing.

Human thymosin beta 4 (TB4) is a small acidic peptide involved in angiogenesis, wound healing, cancer metastasis and cardiac repair. Currently human TB4 is synthesized chemically for research and this is costly. In order to obtain sufficient biologically active human TB4 economically, we cloned and overexpressed this protein in an Escherichia coli system.

PDGF synergistically enhances IFN-gamma-induced expression of CXCL10 in blood-derived macrophages: implications for HIV dementia.

There is increasing cumulative evidence that activated mononuclear phagocytes (macrophages/microglia) releasing inflammatory mediators in the CNS are a better correlate of HIV-associated dementia (HAD) than the actual viral load in the brain. Earlier studies on simian HIV/rhesus macaque model of NeuroAIDS confirmed that pathological changes in brains of macaques with encephalitis were associated with up-regulation of platelet-derived growth factor (PDGF) and the chemokine, CXCL10. Because the complex interplay of inflammatory mediators released by macrophages often leads to the induction of neurotoxins in HAD, we hypothesized that PDGF could interact with IFN-gamma to modulate the expression of CXCL10 in these primary virus target cells.

Human bocavirus infection, People's Republic of China.

A newly identified parvovirus, human bocavirus (HBoV), was found in 21 (8.3%) of 252 nasopharyngeal aspirates from hospitalized children with lower respiratory tract infection in Hunan Province, People's Republic of China. Viral loads were 10(4) to 10(10) copies/mL.

Purification of recombinant human interferon-epsilon and oligonucleotide microarray analysis of interferon-epsilon-regulated genes.

Recently identified interferon-epsilon (IFN-epsilon) belongs to type I interferons. IFN-epsilon is highly and constitutively expressed in the brain, but its biochemical and biological characteristics are poorly understood. In this study, full-length IFN-epsilon cDNA was cloned from human peripheral blood lymphocyte by RT-PCR, and was expressed in Escherichia coli (E.

[Biological activities of recombinant human interferon Epsilon].

Objective: To construct a novel recombinant rhIFN-epsilon155ser, and study its biological activities.

Methods: The whole sequence of rhIFN-epsilon was artificially synthesized and some codons were altered according to the preferred codon using of E.coli.

[Cloning, expression and purification of interferon-kappa, a novel human interferon, and its antiviral activity].

Objective: To prepare human interferon-k (hIFN-kappa) and study its biological activities.

Methods: Whole length of hIFN-kappa's cDNA was cloned, and its sequence was chemically synthesized according to the optimized codons of E.coli, then was expressed in E.