title: beta-Chemokine production by neural and glial progenitor cells is enhanced by HIV-1 Tat: effects on microglial migration.
abstract: Human immunodeficiency virus (HIV)-1 neuropathology results from collective effects of viral proteins and inflammatory mediators on several cell types. Significant damage is mediated indirectly through inflammatory conditions promulgated by glial cells, including microglia that are productively infected by HIV-1, and astroglia. Neural and glial progenitors exist in both developing and adult brains. To determine whether progenitors are targets of HIV-1, a multi-plex assay was performed to assess chemokine/cytokine expression after treatment with viral proteins transactivator of transcription (Tat) or glycoprotein 120 (gp120). In the initial screen, ten analytes were basally released by murine striatal progenitors. The beta-chemokines CCL5/regulated upon activation, normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1alpha, and CCL4/macrophage inflammatory protein-1beta were increased by 12-h exposure to HIV-1 Tat. Secreted factors from Tat-treated progenitors were chemoattractive towards microglia, an effect blocked by 2D7 anti-CCR5 antibody pre-treatment. Tat and opiates have interactive effects on astroglial chemokine secretion, but this interaction did not occur in progenitors. gp120 did not affect chemokine/cytokine release, although both CCR5 and CXCR4, which serve as gp120 co-receptors, were detected in progenitors. We postulate that chemokine production by progenitors may be a normal, adaptive process that encourages immune inspection of newly generated cells. Pathogens such as HIV might usurp this function to create a maladaptive state, especially during development or regeneration, when progenitors are numerous.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0709, USA.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Hahn
authors.forename: Phu
authors.initials: P
authors.lastname: Vo
authors.forename: Sylvia
authors.initials: S
authors.lastname: Fitting
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Block
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Hauser
authors.forename: Pamela E
authors.initials: PE
authors.lastname: Knapp
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D002633:Chemotaxis; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D053610:Opiate Alkaloids / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D053610:Opiate Alkaloids; C514793:gp120 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus
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