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Expression of chemokines by human fetal microglia after treatment with the human immunodeficiency virus type 1 protein Tat

Journal of NeuroVirology volume 10, pages 86–97 (2004)Cite this article

Abstract

Chemokines are important mediators of inflammation. It has been demonstrated that there is an increase in chemokine expression in both the sera and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1). The HIV-1 viral protein, Tat, a transcriptional regulator, has been detected in the central nervous system (CNS) of infected individuals, and has been demonstrated to induce chemokines from various cells within the brain. The authors now show that the interaction of human microglia, the resident phagocytes of the brain, with Tat leads to dramatic increases in the secretion of the chemokines CCL2, CXCL8, CXCL10, CCL3, CCL4, and CCL5. Treatment of microglia with Tat plus specific inhibitors of signal transduction pathways demonstrated that the induction of each chemokine is regulated differently. Tat-induced expression of CCL2 and CCL4 was mediated by the activation of the extracellular regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K) pathway, whereas the induction of CXCL8 and CCL3 was mediated only by the p38 MAPK pathway. Tat-induced CXCL10 expression was mediated, to some extent, by activation of the ERK1/2 MAPK pathway, phosphatidylinositol 3-kinase pathway, and the p38 MAPK pathway, whereas CCL5 expression was not mediated by any pathway tested. Western blot analysis demonstrated phosphorylation of ERK 1/2 and Akt upon stimulation of microglia with Tat. These data suggest that a soluble HIV-1 viral protein can alter the chemokine balance in the brain, which can then lead to an influx of inflammatory cells and contribute to the neuropathogenesis of HIV-1 infection.

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Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, Forchheimer 727, 1300 Morris Park Avenue, 10461, Bronx, NY, USA

    Teresa G. D’Aversa & Joan W. Berman

  2. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA

    Karl O. A. Yu & Joan W. Berman

Authors
  1. Teresa G. D’Aversa
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  2. Karl O. A. Yu
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  3. Joan W. Berman
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Corresponding author

Correspondence to Joan W. Berman.

Additional information

This work was supported by the National Institutes of Mental Health grant MH52974 (JWB), National Institutes of Health grant NS11920 (JWB), and the National Institutes of Health Experimental Neuropathology Training Grant T32NS07098 (TGD).

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D’Aversa, T.G., Yu, K.O.A. & Berman, J.W. Expression of chemokines by human fetal microglia after treatment with the human immunodeficiency virus type 1 protein Tat. Journal of NeuroVirology 10, 86–97 (2004). https://doi.org/10.1080/13550280490279807

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  • DOI: https://doi.org/10.1080/13550280490279807

Keywords

  • CCL2
  • CCL3
  • CCL4
  • CXCL8
  • HIV encephalitis
  • MAP kinases