Gp120-mediated cytotoxicity of human brain microvascular endothelial cells is dependent on p38 mitogen-activated protein kinase activation

Naveed Ahmed Khan, Francescopaolo Di Cello, Monique Stins, Kwang Sik Kim

Research output: Contribution to journalArticle

Abstract

Breakdown of the blood-brain barrier has been shown to contribute to neurological disorders that are prevalent in human immunodeficiency virus type 1 (HIV-1)-infected individuals, but the mechanisms involved in HIV-1-associated blood-brain barrier dysfunction remain incompletely understood. Using human brain microvascular endothelial cells (HBMECs) that constitute the blood-brain barrier, the authors determined the cytotoxic effects of gp120 on HBMECs. The authors showed that gp120 induced cytotoxicity of HBMECs derived from children, which required cotreatment with interferon (IFN)-γ. IFN-γ treatment exhibited up-regulation of the chemokine receptors CCR3 and CCR5 in children's HBMECs. In contrast, HBMECs isolated from adults were not responsive to gp120-mediated cytotoxicity. Peptides of gp120 representing binding regions for CD4 and chemokine receptors as well as CD4 antibody inhibited gp120-mediated cytotoxicity of HBMECs. RANTES, as expected, inhibited M-tropic gp120-mediated HBMEC cytotoxicity, whereas stromal cell-derived factor (SDF)-1α failed to inhibit T-tropic gp120-mediated cytotoxicity. Of interest, gp120 peptides representing non-CD4/non-chemokine receptor binding regions inhibited gp120-mediated HBMEC cytotoxicity. In addition, the authors showed that gp120-mediated HBMEC cytotoxicity involved p38 mitogen-activated protein kinase pathway. Taken together, these findings showed that gp120, in the presence of IFN-γ, can cause dysfunction of the blood-brain barrier endothelium via MAPK pathways involving several gp120-HBMEC interactions.

Original languageEnglish (US)
Pages (from-to)242-251
Number of pages10
JournalJournal of NeuroVirology
Volume13
Issue number3
DOIs
StatePublished - May 2007

Fingerprint

p38 Mitogen-Activated Protein Kinases
Endothelial Cells
Brain
Blood-Brain Barrier
Interferons
Chemokine Receptors
HIV-1
Chemokine CXCL12
Chemokine CCL5
CD4 Antigens
Peptides
Nervous System Diseases
Cell Communication
Endothelium
Up-Regulation
Antibodies

Keywords

  • Blood-brain barrierc
  • Cytotoxicity
  • Gp120
  • Human brain microvascular endothelial cells
  • MAPK

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

Gp120-mediated cytotoxicity of human brain microvascular endothelial cells is dependent on p38 mitogen-activated protein kinase activation. / Khan, Naveed Ahmed; Di Cello, Francescopaolo; Stins, Monique; Kim, Kwang Sik.

In: Journal of NeuroVirology, Vol. 13, No. 3, 05.2007, p. 242-251.

Research output: Contribution to journalArticle

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