The Effect of X4 and R5 HIV-1 on C, C-C, and C-X-C Chemokines during the Early Stages of Infection in Human PBMCs

Wetzel, Michele A.; Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

doi:10.1006/viro.2001.1249

Cited by 37 publications

(28 citation statements)

References 37 publications

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“…Our data and those of others indicate that CXCR3 and CCR5 are maintained or upregulated on HIV-infected leukocytes (Wetzel et al, 2002;Lane et al, 2003) (E.A.E. and J.W.B., unpublished data).…”

Section: Enhanced Hiv-infected Pbmc Transmigration and Bbb Disruptionsupporting

confidence: 82%

CCL2/Monocyte Chemoattractant Protein-1 Mediates Enhanced Transmigration of Human Immunodeficiency Virus (HIV)-Infected Leukocytes across the Blood–Brain Barrier: A Potential Mechanism of HIV–CNS Invasion and NeuroAIDS

Eugenín¹,

Osiecki²,

Lopez³

et al. 2006

J. Neurosci.

349

336

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Section: Enhanced Hiv-infected Pbmc Transmigration and Bbb Disruptionsupporting

confidence: 82%

CCL2/Monocyte Chemoattractant Protein-1 Mediates Enhanced Transmigration of Human Immunodeficiency Virus (HIV)-Infected Leukocytes across the Blood–Brain Barrier: A Potential Mechanism of HIV–CNS Invasion and NeuroAIDS

Eugenín¹,

Osiecki²,

Lopez³

et al. 2006

J. Neurosci.

349

336

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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).…”

Section: Discussionmentioning

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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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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“…The levels of the CCR1͞5 ligands (CCL3 and CCL5), CXCR4 ligands (CXCC12), as well as other critical chemokines (CCL2 and CX3CL1) are increased in a variety of pathological states, including bacterial meningitis (49), lymphocytic choriomeningitis (50), mouse adenovirus (51), herpes simplex virus encephalitis (52), multiple sclerosis (20), cancer (53), and HIV dementia (54) and may account for the increased sensitivity to pain associated with the ''sickness syndrome'' seen in most of these conditions. It should be noted that infection by either R5 or X4 strains of HIV induce the expression of several chemokines, including the chemokine ligands for CCR5 (55,56), and the infection of microglial cells in the brain may provide a source of desensitizing chemokine ligands. Based on the process of heterologous desensitization, chemokine ligands for CXCR4 and CCR1͞5 can apparently inactivate the normal neuronal signaling pathway involved in reducing the sensation of pain.…”

Section: Discussionmentioning

confidence: 99%

Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain

Szabó

Chen²,

Li³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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232

199

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The chemokines use G protein-coupled receptors to regulate the migratory and proadhesive responses of leukocytes. Based on observations that G protein-coupled receptors undergo heterologous desensitization, we have examined the ability of chemokines to also influence the perception of pain by cross-desensitizing opioid G protein-coupled receptors function in vitro and in vivo. We find that the chemotactic activities of both -and ␦-opioid receptors are desensitized following activation of the chemokine receptors CCR5, CCR2, CCR7, and CXCR4 but not of the CXCR1 or CXCR2 receptors. Furthermore, we also find that pretreatment with RAN-TES͞CCL5, the ligand for CCR1, and CCR5 or SDF-1␣͞CXCL12, the ligand for CXCR4, followed by opioid administration into the periaqueductal gray matter of the brain results in an increased rat tail flick response to a painful stimulus. Because chemokine administration into the periaqueductal gray matter inhibits opioidinduced analgesia, we propose that the activation of proinflammatory chemokine receptors down-regulates the analgesic functions of opioid receptors, and this enhances the perception of pain at inflammatory sites. O pioid and chemokine receptors are members of the G i protein-linked seven-transmembrane receptor family. These receptors, as well as the chemokine and endogenous opioid peptide ligands, are widely distributed in brain tissue and the periphery. Chemokines have been classified into four families: C, CC, CXC, and CX 3 C based on the position of conserved cysteines, and they interact with receptors designated CR1, CCR1-11, CXCR1-5, or CX 3 CR1, respectively (1). Three classes of receptors have been identified for the opioids, designated , , and ␦, and each of the opioid receptor genes expressed in brain tissue and immune cells has been cloned and sequenced (2-7).The -, -, and ␦-opioids are known to have inhibitory effects on both antibody and cellular immune responses (8, 9), natural killer cell activity (10), cytokine expression (11-13), and phagocytic activity (14), which may account for the decreased resistance to infections caused by morphine and heroin administration. Furthermore, pretreatment with opioids, including morphine, heroin, met-enkephalin, the selective -agonist ]enkephalin (DPDPE), leads to the inhibition of the chemotactic response of leukocytes to complement-derived chemotactic factors (15) and to the chemokines macrophage inflammatory protein (MIP-1␣)͞CCL3, regulated on activation normal T cell expressed and secreted (RANTES͞CCL5), monocyte chemotactic protein-1 (MCP-1)͞ CCL2, and IL-8͞CXCL8 (16). The latter results suggest that the activation of the -and ␦-opioid receptors leads to the desensitization of the CC chemokine receptor 2 (CCR2) and CXC chemokine receptors CXCR1 and CXCR2. In fact, the latter two receptors are phosphorylated by prior administration of opioids. Moreover, the inhibition of CCL3 and CCL5 responses following opioid pretreatment is consistent with the desensitization of either CCR1 or CCR5, or both. This receptor crosstalk r...

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The Effect of X4 and R5 HIV-1 on C, C-C, and C-X-C Chemokines during the Early Stages of Infection in Human PBMCs

Cited by 37 publications

References 37 publications

CCL2/Monocyte Chemoattractant Protein-1 Mediates Enhanced Transmigration of Human Immunodeficiency Virus (HIV)-Infected Leukocytes across the Blood–Brain Barrier: A Potential Mechanism of HIV–CNS Invasion and NeuroAIDS

CCL2/Monocyte Chemoattractant Protein-1 Mediates Enhanced Transmigration of Human Immunodeficiency Virus (HIV)-Infected Leukocytes across the Blood–Brain Barrier: A Potential Mechanism of HIV–CNS Invasion and NeuroAIDS

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

Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain

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