Skip to main content

Advertisement

Log in

CCL5/RANTES Gene Deletion Attenuates Opioid-Induced Increases in Glial CCL2/MCP-1 Immunoreactivity and Activation in HIV-1 Tat-Exposed Mice

  • Original Article
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

To assess the role of CC-chemokine ligand 5 (CCL5)/RANTES in opiate drug abuse and human immunodeficiency virus type 1 (HIV-1) comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild-type and CCL5 knockout mice. Mice were injected intrastriatally with vehicle or Tat and assessed after 7 days. Morphine was administered to some Tat-injected mice via time-release implant (5 mg/day, s.c. for 5 days) starting at 2 days post injection. Glial activation was significantly reduced in CCL5(−/−) compared to wild-type mice at 7 days following combined Tat and morphine exposure. Moreover, the percentage of 3-nitrotyrosine immunopositive macrophages/microglia was markedly reduced in CCL5(−/−) mice injected with Tat ± morphine compared to wild-type counterparts, suggesting that CCL5 contributes to nitrosative stress in HIV-1 encephalitis. In CCL5(−/−) mice, the reductions in Tat ± morphine-induced gliosis coincided with significant declines in the proportion of CCL2/MCP-1-immunoreactive astrocytes and macrophages/microglia compared to wild-type counterparts. In knockout mice, neither Tat alone nor in combination with morphine increased the proportion of CCL2-immunoreactive astrocytes above percentages seen in vehicle-injected controls. Macrophages/microglia differed showing modest, albeit significant, increases in the proportion of CCL2-positive cells with combined Tat and morphine exposure, suggesting that CCL5 preferentially affects CCL2 expression by astroglia. Thus, CCL5 mediates glial activation caused by Tat and morphine, thereby aggravating HIV-1 neuropathogenesis in opiate abusers and non-abusers. CCL5 is implicated as mediating the cytokine-driven amplification of CCL2 production by astrocytes and resultant macrophage/microglial recruitment and activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adler MW, Geller EB, Rogers TJ, Henderson EE, Eisenstein TK (1993) Opioids, receptors, and immunity. Adv Exp Med Biol 335:13–20

    PubMed  CAS  Google Scholar 

  • Albright AV, Shieh JTC, Itoh T, Lee B, Pleasure D, O’Connor MJ et al (1999) Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates. J Virol 73:205–213

    PubMed  CAS  Google Scholar 

  • Allen SJ, Crown SE, Handel TM (2007) Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 25:787–820

    Article  PubMed  CAS  Google Scholar 

  • Balistreri CR, Caruso C, Grimaldi MP, Listi F, Vasto S, Orlando V, Campagna AM, Lio D, Candore G (2007) CCR5 receptor: biologic and genetic implications in age-related diseases. Ann N Y Acad Sci 1100:162–72

    Article  PubMed  CAS  Google Scholar 

  • Barnes DA, Huston M, Holmes R, Benveniste EN, Yong VW, Scholz P et al (1996) Induction of RANTES expression by astrocytes and astrocytoma cell lines. J Neuroimmunol 71:207–214 doi:10.1016/S0165-5728(96)00154-3

    Article  PubMed  CAS  Google Scholar 

  • Benveniste EN, Benos DJ (1995) TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. FASEB J 9:1577–1584

    PubMed  CAS  Google Scholar 

  • Benveniste EN, Tang LP, Law RM (1995) Differential regulation of astrocyte TNF-alpha expression by the cytokines TGF-beta, IL-6 and IL-10. Int J Dev Neurosci 13:341–349 doi:10.1016/0736-5748(94)00061-7

    Article  PubMed  CAS  Google Scholar 

  • Bidlack JM (2000) Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol 7:719–723 doi:10.1128/CDLI.7.5.719-723.2000

    Article  PubMed  CAS  Google Scholar 

  • Bidlack JM, Khimich M, Parkhill AL, Sumagin S, Sun B, Tipton CM (2006) Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol 1:260–269 doi:10.1007/s11481-006-9026-2

    Article  PubMed  Google Scholar 

  • Boutet A, Salim H, Taoufik Y, Lledo PM, Vincent JD, Delfraissy JF et al (2001) Isolated human astrocytes are not susceptible to infection by M- and T-tropic HIV-1 strains despite functional expression of the chemokine receptors CCR5 and CXCR4. Glia 34:165–177 doi:10.1002/glia.1051

    Article  PubMed  CAS  Google Scholar 

  • Bruce-Keller AJ, Turchan-Cholewo J, Smart EJ, Guerin T, Chauhan A, Reid R et al (2008) Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 Tat transgenic mice. Glia 56:1414–1427 doi:10.1002/glia.20708

    Google Scholar 

  • Carr DJ, Rogers TJ, Weber RJ (1996) The relevance of opioids and opioid receptors on immunocompetence and immune homeostasis. Proc Soc Exp Biol Med 213:248–257

    PubMed  CAS  Google Scholar 

  • Carr DJ, Serou M (1995) Exogenous and endogenous opioids as biological response modifiers. Immunopharmacology 31:59–71 doi:10.1016/0162-3109(95)00033-6

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, St HC, Conant K (2004) Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients. Antivir Ther 9:431–440

    PubMed  CAS  Google Scholar 

  • Chen C, Li J, Bot G, Szabo I, Rogers TJ, Liu-Chen LY (2004) Heterodimerization and cross-desensitization between the mu-opioid receptor and the chemokine CCR5 receptor. Eur J Pharmacol 483:175–186 doi:10.1016/j.ejphar.2003.10.033

    Article  PubMed  CAS  Google Scholar 

  • Chung IY, Benveniste EN (1990) Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J Immunol 144:2999–3007

    PubMed  CAS  Google Scholar 

  • Conant K, Garzino-Demo A, Nath A, McArthur JC, Halliday W, Power C et al (1998) Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci USA 95:3117–3121 doi:10.1073/pnas.95.6.3117

    Article  PubMed  CAS  Google Scholar 

  • Donahoe RM, Vlahov D (1998) Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77–87 doi:10.1016/S0165-5728(97)00224-5

    Article  PubMed  CAS  Google Scholar 

  • Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180–190 doi:10.1002/glia.1107

    Article  PubMed  CAS  Google Scholar 

  • Dorf ME, Berman MA, Tanabe S, Heesen M, Luo Y (2000) Astrocytes express functional chemokine receptors. J Neuroimmunol 111:109–121 doi:10.1016/S0165-5728(00)00371-4

    Article  PubMed  CAS  Google Scholar 

  • Edinger AL, Mankowski JL, Doranz BJ, Margulies BJ, Lee B, Rucker J et al (1997) CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc Natl Acad Sci USA 94:14742–14747 doi:10.1073/pnas.94.26.14742

    Article  PubMed  CAS  Google Scholar 

  • Eisenstein TK, Hilburger ME (1998) Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol 83:36–44 doi:10.1016/S0165-5728(97)00219-1

    Article  PubMed  CAS  Google Scholar 

  • El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF (2005) Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia 50:91–106 doi:10.1002/glia.20148

    Article  PubMed  Google Scholar 

  • El-Hage N, Wu G, Ambati J, Bruce-Keller AJ, Knapp PE, Hauser KF (2006a) CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates. J Neuroimmunol 178:9–16 doi:10.1016/j.jneuroim.2006.05.027

    Article  PubMed  CAS  Google Scholar 

  • El-Hage N, Wu G, Wang J, Ambati J, Knapp PE, Reed JL et al (2006b) HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines. Glia 53:132–146 doi:10.1002/glia.20262

    Article  PubMed  Google Scholar 

  • Eriksson PS, Hansson E, Rönnbäck L (1991) Mu and delta opiate receptors in neuronal and astroglial primary cultures from various regions of the brain-coupling with adenylate cyclase, localisation on the same neurones and association with dopamine (D1) receptor adenylate cyclase. Neuropharmacology 30:1233–1239 doi:10.1016/0028-3908(91)90170-G

    Article  PubMed  CAS  Google Scholar 

  • Ethisham A, Nath A, Greene-Avison R, Schmitt FA, Bales RA, Avison MJ et al (2004) Inflammatory changes and breakdown of microvascular integrity in early human immunodeficiency virus dementia. J Neurovirol 10:223–232 doi:10.1080/13550280490463532

    Article  PubMed  CAS  Google Scholar 

  • Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW (2006) 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. J Neurosci 26:1098–1106 doi:10.1523/JNEUROSCI.3863-05.2006

    Article  PubMed  CAS  Google Scholar 

  • Falsig J, Porzgen P, Lund S, Schrattenholz A, Leist M (2006) The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function. J Neurochem 96:893–907 doi:10.1111/j.1471-4159.2005.03622.x

    Article  PubMed  CAS  Google Scholar 

  • Ghirnikar RS, Lee YL, He TR, Eng LF (1996) Chemokine expression in rat stab wound brain injury. J Neurosci Res 46:727–733 doi:10.1002/(SICI)1097-4547(19961215)46:6<727::AID-JNR9>3.0.CO;2-H

    Article  PubMed  CAS  Google Scholar 

  • Glass WG, Rosenberg HF, Murphy PM (2003) Chemokine regulation of inflammation during acute viral infection. Curr Opin Allergy Clin Immunol 3:467–473 doi:10.1097/00130832-200312000-00008

    Article  PubMed  CAS  Google Scholar 

  • Guo H, Jin YX, Ishikawa M, Huang YM, Van der Meide PH, Link H et al (1998) Regulation of beta-chemokine mRNA expression in adult rat astrocytes by lipopolysaccharide, proinflammatory and immunoregulatory cytokines. Scand J Immunol 48:502–508 doi:10.1046/j.1365-3083.1998.00422.x

    Article  PubMed  CAS  Google Scholar 

  • Gurwell JA, Nath A, Sun Q, Zhang J, Martin KM, Chen Y et al (2001) Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. Neuroscience 102:555–563 doi:10.1016/S0306-4522(00)00461-9

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, El-Hage N, Buch S, Tyor WR, Nath A, Bruce-Keller AJ et al (2006) Impact of opiate-HIV-1 interactions on neurotoxic signaling. J Neuroimmune Pharmacol 1:98–105 doi:10.1007/s11481-005-9000-4

    Article  PubMed  Google Scholar 

  • Hauser KF, El-Hage N, Stiene-Martin A, Maragos WF, Nath A, Persidsky Y et al (2007) HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse. J Neurochem 100:567 doi:10.1111/j.1471-4159.2006.04227.x

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, Stiene-Martin A, Mattson MP, Elde RP, Ryan SE, Godleske CC (1996) μ-Opioid receptor-induced Ca2+ mobilization and astroglial development: Morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca2+-dependent mechanism. Brain Res 720:191–203 doi:10.1016/0006-8993(96)00103-5

    Article  PubMed  CAS  Google Scholar 

  • Hemmick LM, Bidlack JM (1991) Endorphin peptides enhance mitogen-induced T cell proliferation which has been suppressed by prostaglandins. Adv Exp Med Biol 288:211–214

    PubMed  CAS  Google Scholar 

  • Janabi N, Di SM, Wallon C, Hery C, Chiodi F, Tardieu M (1998) Induction of human immunodeficiency virus type 1 replication in human glial cells after proinflammatory cytokines stimulation: effect of IFNgamma, IL1beta, and TNFalpha on differentiation and chemokine production in glial cells. Glia 23:304–315 doi:10.1002/(SICI)1098-1136(199808)23:4<304::AID-GLIA3>3.0.CO;2-2

    Article  PubMed  CAS  Google Scholar 

  • Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988–994 doi:10.1038/35073667

    Article  PubMed  CAS  Google Scholar 

  • Kelder W, McArthur J, Nance-Sproson T, McCleron D, Griffin D (1998) Beta-chemokines MCP-1 and RANTES are selectively increased in the cerebral spinal fluid with human immunodeficiency virus-associated dementia. Ann Neurol 44:831–835 doi:10.1002/ana.410440521

    Article  PubMed  CAS  Google Scholar 

  • Kielstein A, Tsikas D, Galloway GP, Mendelson JE (2007) Asymmetric dimethylarginine (ADMA)—a modulator of nociception in opiate tolerance and addiction? Nitric Oxide 17:55–59 doi:10.1016/j.niox.2007.05.005

    Article  PubMed  CAS  Google Scholar 

  • Kim MO, Suh HS, Brosnan CF, Lee SC (2004) Regulation of RANTES/CCL5 expression in human astrocytes by interleukin-1 and interferon-beta. J Neurochem 90:297–308 doi:10.1111/j.1471-4159.2004.02487.x

    Article  PubMed  CAS  Google Scholar 

  • Kitai R, Zhao ML, Zhang N, Hua LL, Lee SC (2000) Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta. J Neuroimmunol 110:230–239 doi:10.1016/S0165-5728(00)00315-5

    Article  PubMed  CAS  Google Scholar 

  • Klein RS, Williams KC, Alvarez-Hernandez X, Westmoreland S, Force T, Lackner AA, Luster AD (1999) Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J Immunol 163:1636–1646

    PubMed  CAS  Google Scholar 

  • Kutsch O, Oh J, Nath A, Benveniste EN (2000) Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol 74:9214–9221 doi:10.1128/JVI.74.19.9214-9221.2000

    Article  PubMed  CAS  Google Scholar 

  • Lee HP, Jun YC, Choi JK, Kim JI, Carp RI, Kim YS (2005) The expression of RANTES and chemokine receptors in the brains of scrapie-infected mice. J Neuroimmunol 158:26–33 doi:10.1016/j.jneuroim.2004.08.010

    Article  PubMed  CAS  Google Scholar 

  • Li W, Malpica-Llanos TM, Gundry R, Cotter RJ, Sacktor N, McArthur J, Nath A (2008) Nitrosative stress with HIV dementia causes decreased l-prostaglandin D synthase activity. Neurology 70:1753–1762

    Article  PubMed  CAS  Google Scholar 

  • Lloyd CM, Phillips AR, Cooper GJ, Dunbar PR (2008) Three-colour fluorescence immunohistochemistry reveals the diversity of cells staining for macrophage markers in murine spleen and liver. J Immunol Methods 334:70–81 doi:10.1016/j.jim.2008.02.005

    Article  PubMed  CAS  Google Scholar 

  • Luo Y, Berman MA, Abromson-Leeman SR, Dorf ME (2003) Tumor necrosis factor is required for RANTES-induced astrocyte monocyte chemoattractant protein-1 production. Glia 43:119–127 doi:10.1002/glia.10231

    Article  PubMed  Google Scholar 

  • Luo Y, Berman MA, Zhai Q, Fischer FR, Abromson-Leeman SR, Zhang Y et al (2002) RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes. Glia 39:19–30 doi:10.1002/glia.10079

    Article  PubMed  Google Scholar 

  • Luo Y, Fischer FR, Hancock WW, Dorf ME (2000) Macrophage inflammatory protein-2 and KC induce chemokine production by mouse astrocytes. J Immunol 165:4015–4023

    PubMed  CAS  Google Scholar 

  • Machelska H, Stein C (2006) Leukocyte-derived opioid peptides and inhibition of pain. J Neuroimmune Pharmacol 1:90–97 doi:10.1007/s11481-005-9002-2

    Article  PubMed  Google Scholar 

  • Mahad DJ, Ransohoff RM (2003) The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin Immunol 15:23–32 doi:10.1016/S1044-5323(02)00125-2

    Article  PubMed  CAS  Google Scholar 

  • Mahajan SD, Aalinkeel R, Reynolds JL, Nair BB, Fernandez SF, Schwartz SA et al (2005) Morphine exacerbates HIV-1 viral protein gp120 induced modulation of chemokine gene expression in U373 astrocytoma cells. Curr HIV Res 3:277–288 doi:10.2174/1570162054368048

    Article  PubMed  CAS  Google Scholar 

  • Makino Y, Cook DN, Smithies O, Hwang OY, Neilson EG, Turka LA et al (2002) Impaired T cell function in RANTES-deficient mice. Clin Immunol 102:302–309 doi:10.1006/clim.2001.5178

    Article  PubMed  CAS  Google Scholar 

  • Mankowski JL, Queen SE, Clements JE, Zink MC (2004) Cerebrospinal fluid markers that predict SIV CNS disease. J Neuroimmunol 157:66–70 doi:10.1016/j.jneuroim.2004.08.031

    Article  PubMed  CAS  Google Scholar 

  • McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 62:111–123 doi:10.1016/S0376-8716(00)00181-2

    Article  PubMed  CAS  Google Scholar 

  • McManus CM, Weidenheim K, Woodman SE, Nunez J, Hesselgesser J, Nath A et al (2000) Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation. Am J Pathol 156:1441–1453

    PubMed  CAS  Google Scholar 

  • Miller MD, Krangel MS (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 12:17–46

    PubMed  CAS  Google Scholar 

  • Miller RJ, Meucci O (1999) AIDS and the brain: is there a chemokine connection? Trends Neurosci 22:471–479 doi:10.1016/S0166-2236(99)01408-3

    Article  PubMed  CAS  Google Scholar 

  • Muscoli C, Cuzzocrea S, Ndengele MM, Mollace V, Porreca F, Fabrizi F et al (2007) Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice. J Clin Invest 117:3530–3539 doi:10.1172/JCI32420

    Article  PubMed  CAS  Google Scholar 

  • Nath A (1999) Pathobiology of human immunodeficiency virus dementia. Semin Neurol 19:113–127

    Article  PubMed  CAS  Google Scholar 

  • Norris JG, Tang L, Sparacio SM, Benveniste EN (1994) Signal transduction pathways mediating astrocyte IL-6 induction by IL-1β induction by IL-1β and tumor necrosis factor-α. J Immunol 152:841–850

    PubMed  CAS  Google Scholar 

  • Nyland SB, Specter S, Im-Sin J, Ugen KE (1998) Opiate effects on in vitro human retroviral infection. Adv Exp Med Biol 437:91–100

    PubMed  CAS  Google Scholar 

  • Oh JW, Schwiebert LM, Benveniste EN (1999) Cytokine regulation of CC and CXC chemokine expression by human astrocytes. J Neurovirol 5:82–94 doi:10.3109/13550289909029749

    Article  PubMed  CAS  Google Scholar 

  • Overholser ED, Coleman GD, Bennett JL, Casaday RJ, Zink MC, Barber SA et al (2003) Expression of simian immunodeficiency virus (SIV) nef in astrocytes during acute and terminal infection and requirement of nef for optimal replication of neurovirulent SIV in vitro. J Virol 77:6855–6866 doi:10.1128/JVI.77.12.6855-6866.2003

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH Jr (1990) Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 4:869–874 doi:10.1097/00002030-199009000-00006

    Article  PubMed  CAS  Google Scholar 

  • Rahim RT, Meissler JJ, Zhang L, Adler MW, Rogers TJ, Eisenstein TK (2003) Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules. J Neuroimmunol 144:16–27 doi:10.1016/S0165-5728(03)00273-X

    Article  PubMed  CAS  Google Scholar 

  • Ransohoff RM, Liu L, Cardona AE (2007) Chemokines and chemokine receptors: multipurpose players in neuroinflammation. Int Rev Neurobiol 82:187–204

    Article  PubMed  CAS  Google Scholar 

  • Rogers TJ, Peterson PK (2003) Opioid G protein-coupled receptors: signals at the crossroads of inflammation. Trends Immunol 24:116–121 doi:10.1016/S1471-4906(03)00003-6

    Article  PubMed  CAS  Google Scholar 

  • Rogers TJ, Steele AD, Howard OM, Oppenheim JJ (2000) Bidirectional heterologous desensitization of opioid and chemokine receptors. Ann N Y Acad Sci 917:19–28

    PubMed  CAS  Google Scholar 

  • Roy S, Wang J, Kelschenbach J, Koodie L, Martin J (2006) Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol 1:77–89 doi:10.1007/s11481-005-9009-8

    Article  PubMed  Google Scholar 

  • Ryu JK, McLarnon JG (2006) Minocycline or iNOS inhibition block 3-nitrotyrosine increases and blood–brain barrier leakiness in amyloid beta-peptide-injected rat hippocampus. Exp Neurol 198:552–557 doi:10.1016/j.expneurol.2005.12.016

    Article  PubMed  CAS  Google Scholar 

  • Sanders VJ, Pittman CA, White MG, Wang G, Wiley CA, Achim CL (1998) Chemokines and receptors in HIV encephalitis. AIDS 12:1021–1026 doi:10.1097/00002030-199809000-00008

    Article  PubMed  CAS  Google Scholar 

  • Sasseville VG, Smith MM, Mackay DR, Pauley DR, Mansfield KG, Ringler DJ et al (1996) Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis. Am J Pathol 149:1459–1467

    PubMed  CAS  Google Scholar 

  • Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K et al (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63:2084–2090

    PubMed  CAS  Google Scholar 

  • Sharp BM (2006) Multiple opioid receptors on immune cells modulate intracellular signaling. Brain Behav Immun 20:9–14 doi:10.1016/j.bbi.2005.02.002

    Article  PubMed  CAS  Google Scholar 

  • Sharp BM, Gekker G, Li MD, Chao CC, Peterson PK (1998) Delta-opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). Biochem Pharmacol 56:289–292 doi:10.1016/S0006-2952(98)00155-5

    Article  PubMed  CAS  Google Scholar 

  • Shavali S, Combs CK, Ebadi M (2006) Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronal cells in co-culture: relevance to Parkinson’s disease. Neurochem Res 31:85–94 doi:10.1007/s11064-005-9233-x

    Article  PubMed  CAS  Google Scholar 

  • Stiene-Martin A, Hauser KF (1991) Glial growth is regulated by agonists selective for multiple opioid receptor types in vitro. J Neurosci Res 29:538–548 doi:10.1002/jnr.490290415

    Article  PubMed  CAS  Google Scholar 

  • Stiene-Martin A, Knapp PE, Martin KM, Gurwell JA, Ryan S, Thornton SR et al (2001) Opioid system diversity in developing neurons, astroglia, and oligodendroglia in the subventricular zone and striatum: impact on gliogenesis in vivo. Glia 36:78–88 doi:10.1002/glia.1097

    Article  PubMed  CAS  Google Scholar 

  • Stiene-Martin A, Zhou R, Hauser KF (1998) Regional, developmental, and cell cycle-dependent differences in μ, δ, and κ-opioid receptor expression among cultured mouse astrocytes. Glia 22:249–259 doi:10.1002/(SICI)1098-1136(199803)22:3<249::AID-GLIA4>3.0.CO;2-0

    Article  PubMed  CAS  Google Scholar 

  • Sun D, Hu X, Liu X, Whitaker JN, Walker WS (1997) Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells. J Neurosci Res 48:192–200 doi:10.1002/(SICI)1097-4547(19970501)48:3<192::AID-JNR2>3.0.CO;2-A

    Article  PubMed  CAS  Google Scholar 

  • Szabo I, Chen XH, Xin L, Adler MW, Howard OM, Oppenheim JJ et al (2002) Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc Natl Acad Sci USA 99:10276–10281 doi:10.1073/pnas.102327699

    Article  PubMed  CAS  Google Scholar 

  • Szabo I, Wetzel MA, Zhang N, Steele AD, Kaminsky DE, Chen C et al (2003) Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization. J Leukoc Biol 74:1074–1082 doi:10.1189/jlb.0203067

    Article  PubMed  CAS  Google Scholar 

  • Turchan-Cholewo J, Dimayuga FO, Ding Q, Keller JN, Hauser KF, Knapp PE et al (2008) Cell-specific actions of HIV-Tat and morphine on opioid receptor expression in glia. J Neurosci Res 86:2100–2110 doi:10.1002/jnr.21653

    Article  PubMed  CAS  Google Scholar 

  • Vago L, Nebuloni M, Bonetto S, Pellegrinelli A, Zerbi P, Ferri A et al (2001) Rantes distribution and cellular localization in the brain of HIV-infected patients. Clin Neuropathol 20:139–145

    PubMed  CAS  Google Scholar 

  • Westmoreland SV, Rottman JB, Williams KC, Lackner AA, Sasseville VG (1998) Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis. Am J Pathol 152:659–665

    PubMed  CAS  Google Scholar 

  • Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165:6519–6524

    PubMed  CAS  Google Scholar 

  • Zhang Y, Zhai Q, Luo Y, Dorf ME (2002) RANTES-mediated chemokine transcription in astrocytes involves activation and translocation of p90 ribosomal S6 protein kinase (RSK). J Biol Chem 277:19042–19048 doi:10.1074/jbc.M112442200

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants DA19398 and P20RR015592. We thank Dr. Avindra Nath for providing HIV-1 Tat protein and expert guidance, and Dr. Guanghan Wu and Mr. Kenneth Martin for expert technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kurt F. Hauser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

El-Hage, N., Bruce-Keller, A.J., Knapp, P.E. et al. CCL5/RANTES Gene Deletion Attenuates Opioid-Induced Increases in Glial CCL2/MCP-1 Immunoreactivity and Activation in HIV-1 Tat-Exposed Mice. J Neuroimmune Pharmacol 3, 275–285 (2008). https://doi.org/10.1007/s11481-008-9127-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-008-9127-1

Keywords

Navigation