Upregulated expression of interleukin-8, RANTES and chemokine receptors in human astrocytic cells infected with HIV-1

Manuela Cota, Andrea Kleinschmidt, Francesca Ceccherini-Silberstein, Francesca Aloisi, Manuela Mengozzi, Alberto Mantovani, Ruth Brack-Werner, Guido Poli

Research output: Contribution to journalArticle

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Abstract

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) affects primarily microglial cells and astrocytes. Infection of these latter cells occurs independently of CD4 and is characterised by preferential accumulation of 2 Kb mRNA, encoding mostly Nef, and by low levels of 4.5 and 9 Kb RNAs. We have investigated the potential role of chronic HIV infection of human astrocytic cells on the expression of pro-inflammatory cytokines, chemokines and their receptors by comparing the infected TH4-7-5 with its parental uninfected 85HG66 cell lines. Upregulated levels of tumour necrosis factor-α (TNF-α) and of certain chemokines, namely interleukin-8 (IL-8) and regulated upon activation normal T cell expressed and secreted (RANTES), were observed in the infected versus uninfected cells, whereas monocyte chemotactic protein-1 (MCP-1) was comparably expressed in both cell lines. This pattern of expression was confirmed in primary foetal astrocytes transiently transfected with HIV. In addition, CXCR1, CXCR2 and CCR2b, receptors for IL-8 and MCP-1, respectively, were also found to be upregulated in TH4-7-5 versus 85HG66. CXCR4, the receptor of stromal cell derived factor-1 (SDF-1) and co-receptor for syncytium inducing HIVs, was comparably expressed in infected and uninfected astrocytic cells, whereas CCR5 was not detected in either cell line. Furthermore, treatment of TH4-7-5 cells with TNF-α or IL-1β stimulated RNA and protein secretion of IL-8, MCP-1, and RANTES as well as HIV expression. Thus, our findings suggest that HIV infection of astrocytic cells can contribute to the establishment of a chronic inflammatory state in the CNS, eventually resulting in HIV encephalitis, by increasing the secretion of pro-inflammatory cytokines, such as TNF-α and several chemokines. Overexpression of chemokine receptors including CCR2b, CXCR1 and CXCR2 in infected astrocytic cells may contribute to HIV-induced damage of the CNS via autocrine/paracrine activation of astrocytes.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalJournal of NeuroVirology
Volume6
Issue number1
Publication statusPublished - 2000

Fingerprint

Chemokine Receptors
Interleukin-8
HIV-1
HIV
T-Lymphocytes
Chemokine CCL2
Virus Diseases
Astrocytes
Central Nervous System
Tumor Necrosis Factor-alpha
Chemokines
Cell Line
Interleukin-8B Receptors
CCR2 Receptors
RNA
Cytokines
CXCR4 Receptors
Chemokine CXCL12
Encephalitis
Giant Cells

Keywords

  • Astrocytes
  • Chemokine receptors
  • Chemokines
  • Cytokines
  • HIV

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

Upregulated expression of interleukin-8, RANTES and chemokine receptors in human astrocytic cells infected with HIV-1. / Cota, Manuela; Kleinschmidt, Andrea; Ceccherini-Silberstein, Francesca; Aloisi, Francesca; Mengozzi, Manuela; Mantovani, Alberto; Brack-Werner, Ruth; Poli, Guido.

In: Journal of NeuroVirology, Vol. 6, No. 1, 2000, p. 75-83.

Research output: Contribution to journalArticle

Cota, M, Kleinschmidt, A, Ceccherini-Silberstein, F, Aloisi, F, Mengozzi, M, Mantovani, A, Brack-Werner, R & Poli, G 2000, 'Upregulated expression of interleukin-8, RANTES and chemokine receptors in human astrocytic cells infected with HIV-1', Journal of NeuroVirology, vol. 6, no. 1, pp. 75-83.
Cota, Manuela ; Kleinschmidt, Andrea ; Ceccherini-Silberstein, Francesca ; Aloisi, Francesca ; Mengozzi, Manuela ; Mantovani, Alberto ; Brack-Werner, Ruth ; Poli, Guido. / Upregulated expression of interleukin-8, RANTES and chemokine receptors in human astrocytic cells infected with HIV-1. In: Journal of NeuroVirology. 2000 ; Vol. 6, No. 1. pp. 75-83.
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AU - Cota, Manuela

AU - Kleinschmidt, Andrea

AU - Ceccherini-Silberstein, Francesca

AU - Aloisi, Francesca

AU - Mengozzi, Manuela

AU - Mantovani, Alberto

AU - Brack-Werner, Ruth

AU - Poli, Guido

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N2 - Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) affects primarily microglial cells and astrocytes. Infection of these latter cells occurs independently of CD4 and is characterised by preferential accumulation of 2 Kb mRNA, encoding mostly Nef, and by low levels of 4.5 and 9 Kb RNAs. We have investigated the potential role of chronic HIV infection of human astrocytic cells on the expression of pro-inflammatory cytokines, chemokines and their receptors by comparing the infected TH4-7-5 with its parental uninfected 85HG66 cell lines. Upregulated levels of tumour necrosis factor-α (TNF-α) and of certain chemokines, namely interleukin-8 (IL-8) and regulated upon activation normal T cell expressed and secreted (RANTES), were observed in the infected versus uninfected cells, whereas monocyte chemotactic protein-1 (MCP-1) was comparably expressed in both cell lines. This pattern of expression was confirmed in primary foetal astrocytes transiently transfected with HIV. In addition, CXCR1, CXCR2 and CCR2b, receptors for IL-8 and MCP-1, respectively, were also found to be upregulated in TH4-7-5 versus 85HG66. CXCR4, the receptor of stromal cell derived factor-1 (SDF-1) and co-receptor for syncytium inducing HIVs, was comparably expressed in infected and uninfected astrocytic cells, whereas CCR5 was not detected in either cell line. Furthermore, treatment of TH4-7-5 cells with TNF-α or IL-1β stimulated RNA and protein secretion of IL-8, MCP-1, and RANTES as well as HIV expression. Thus, our findings suggest that HIV infection of astrocytic cells can contribute to the establishment of a chronic inflammatory state in the CNS, eventually resulting in HIV encephalitis, by increasing the secretion of pro-inflammatory cytokines, such as TNF-α and several chemokines. Overexpression of chemokine receptors including CCR2b, CXCR1 and CXCR2 in infected astrocytic cells may contribute to HIV-induced damage of the CNS via autocrine/paracrine activation of astrocytes.

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