MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis

Eliseo Eugenin, T. G. D'Aversa, L. Lopez, T. M. Calderon, Joan W. Berman

Research output: Contribution to journalArticle

236 Citations (Scopus)

Abstract

Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

Original languageEnglish (US)
Pages (from-to)1299-1311
Number of pages13
JournalJournal of Neurochemistry
Volume85
Issue number5
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

N-Methylaspartate
Astrocytes
T-cells
Neurons
Chemical activation
HIV
Apoptosis
T-Lymphocytes
Poisons
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Protective Agents
Chemokine CCL2
Macrophages
Neurotoxins
Viruses
Chemokines
Infiltration
Dementia

Keywords

  • Apoptosis
  • Glutamate
  • HIV-1
  • MCP-1
  • MK801
  • RANTES

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. / Eugenin, Eliseo; D'Aversa, T. G.; Lopez, L.; Calderon, T. M.; Berman, Joan W.

In: Journal of Neurochemistry, Vol. 85, No. 5, 01.06.2003, p. 1299-1311.

Research output: Contribution to journalArticle

Eugenin, Eliseo ; D'Aversa, T. G. ; Lopez, L. ; Calderon, T. M. ; Berman, Joan W. / MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. In: Journal of Neurochemistry. 2003 ; Vol. 85, No. 5. pp. 1299-1311.
@article{b15395dc785f4ff2b5e6ef5df193a248,
title = "MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis",
abstract = "Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.",
keywords = "Apoptosis, Glutamate, HIV-1, MCP-1, MK801, RANTES",
author = "Eliseo Eugenin and D'Aversa, {T. G.} and L. Lopez and Calderon, {T. M.} and Berman, {Joan W.}",
year = "2003",
month = "6",
day = "1",
doi = "10.1046/j.1471-4159.2003.01775.x",
language = "English (US)",
volume = "85",
pages = "1299--1311",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis

AU - Eugenin, Eliseo

AU - D'Aversa, T. G.

AU - Lopez, L.

AU - Calderon, T. M.

AU - Berman, Joan W.

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

AB - Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

KW - Apoptosis

KW - Glutamate

KW - HIV-1

KW - MCP-1

KW - MK801

KW - RANTES

UR - http://www.scopus.com/inward/record.url?scp=0038579653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038579653&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.2003.01775.x

DO - 10.1046/j.1471-4159.2003.01775.x

M3 - Article

C2 - 12753088

AN - SCOPUS:0038579653

VL - 85

SP - 1299

EP - 1311

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -