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 Zheng, Anuja Ghorpade, Yuri Persidsky, Kimberly A. Carlson, Howard E. Gendelman

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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.

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

Keywords

  • AIDS
  • Brain slices
  • Chemokine
  • Hippocampus

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    Xiong, H., Boyle, J., Winkelbauer, M., Gorantla, S., Zheng, J., Ghorpade, A., Persidsky, Y., Carlson, K. A., & Gendelman, H. E. (2003). Inhibition of long-term potentiation by interleukin-8: Implications for human immunodeficiency virus-1-associated dementia. Journal of Neuroscience Research, 71(4), 600-607. https://doi.org/10.1002/jnr.10503