Inhibition of long-term potentiation by interleukin-8

Implications for human immunodeficiency virus-1-associated dementia

Huangui Xiong, Jeffery Boyle, Matthew Winkelbauer, Santhi Gorantla, Jialin C Zheng, Anuja Ghorpade, Yuri Persidsky, Kim A Carlson, Howard Eliot Gendelman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1)-infected mononuclear phagocytes (MP; brain macrophages and microglia) secrete a number of toxic factors that affect the pathogenesis of HIV-1-associated dementia (HAD). The identification and relative role of each MP toxin for neuronal dysfunction during HAD are not well understood. Interleukin-8 (IL-8), a CXC chemokine involved in leukocyte activation and chemotaxis, is constitutively produced by MP, and elevated levels of IL-8 mRNA were detected in the brains of patients with HIV-1 encephalitis (HIVE) by both ribonuclease protection assays and real-time PCR. To determine the role that IL-8 might play in the neuronal dysfunction in HAD, we studied its effect on synaptic transmission and plasticity in the CA1 region of hippocampus, the seat of learning and memory. Bath application of IL-8 (50 ng/ml) to rat hippocampal slices had no effect on basal synaptic transmission. However, IL-8 was shown to inhibit long-term potentiation (LTP) in a concentration-dependent manner. In control and IL-8-treated slices, the LTP magnitudes were 167.8% ± 11.9% (mean ± SE; n = 17) and 122.2% ± 16.2% of basal levels (n = 13), respectively. These differences were statistically significant (P < 0.05). Preincubation of hippocampal slices with a monoclonal CXCR2 antibody (2 μg/ml) but not control IgG (2 μg/ml) blocked IL-8-induced inhibition of LTP. The expression of CXCR2 receptors in the CA1 region was shown by Western blot assays. The induction of IL-8 in HAD, its inhibition of LTP, and the expression of its receptor, CXCR2, in the hippocampus all suggest that it plays a role in the cognitive dysfunction associated with HAD.

Original languageEnglish (US)
Pages (from-to)600-607
Number of pages8
JournalJournal of Neuroscience Research
Volume71
Issue number4
DOIs
StatePublished - Feb 15 2003

Fingerprint

Long-Term Potentiation
Interleukin-8
Dementia
HIV-1
Interleukin-8B Receptors
Synaptic Transmission
Hippocampus
Leukocyte Chemotaxis
CXC Chemokines
Neuronal Plasticity
Inhibition (Psychology)
Poisons
Brain
Microglia
Encephalitis
Phagocytes
Ribonucleases
Baths
Real-Time Polymerase Chain Reaction
Immunoglobulin G

Keywords

  • AIDS
  • Brain slices
  • Chemokine
  • Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition of long-term potentiation by interleukin-8 : Implications for human immunodeficiency virus-1-associated dementia. / Xiong, Huangui; Boyle, Jeffery; Winkelbauer, Matthew; Gorantla, Santhi; Zheng, Jialin C; Ghorpade, Anuja; Persidsky, Yuri; Carlson, Kim A; Gendelman, Howard Eliot.

In: Journal of Neuroscience Research, Vol. 71, No. 4, 15.02.2003, p. 600-607.

Research output: Contribution to journalArticle

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abstract = "Human immunodeficiency virus type 1 (HIV-1)-infected mononuclear phagocytes (MP; brain macrophages and microglia) secrete a number of toxic factors that affect the pathogenesis of HIV-1-associated dementia (HAD). The identification and relative role of each MP toxin for neuronal dysfunction during HAD are not well understood. Interleukin-8 (IL-8), a CXC chemokine involved in leukocyte activation and chemotaxis, is constitutively produced by MP, and elevated levels of IL-8 mRNA were detected in the brains of patients with HIV-1 encephalitis (HIVE) by both ribonuclease protection assays and real-time PCR. To determine the role that IL-8 might play in the neuronal dysfunction in HAD, we studied its effect on synaptic transmission and plasticity in the CA1 region of hippocampus, the seat of learning and memory. Bath application of IL-8 (50 ng/ml) to rat hippocampal slices had no effect on basal synaptic transmission. However, IL-8 was shown to inhibit long-term potentiation (LTP) in a concentration-dependent manner. In control and IL-8-treated slices, the LTP magnitudes were 167.8{\%} ± 11.9{\%} (mean ± SE; n = 17) and 122.2{\%} ± 16.2{\%} of basal levels (n = 13), respectively. These differences were statistically significant (P < 0.05). Preincubation of hippocampal slices with a monoclonal CXCR2 antibody (2 μg/ml) but not control IgG (2 μg/ml) blocked IL-8-induced inhibition of LTP. The expression of CXCR2 receptors in the CA1 region was shown by Western blot assays. The induction of IL-8 in HAD, its inhibition of LTP, and the expression of its receptor, CXCR2, in the hippocampus all suggest that it plays a role in the cognitive dysfunction associated with HAD.",
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AU - Gorantla, Santhi

AU - Zheng, Jialin C

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AU - Gendelman, Howard Eliot

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