Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids

Santhi Gorantla, Edward Makarov, Deepa Roy, Jennifer Finke-Dwyer, L. Charles Murrin, Howard Eliot Gendelman, Larisa Y Poluektova

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood-brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.

Original languageEnglish (US)
Pages (from-to)456-468
Number of pages13
JournalJournal of Neuroimmune Pharmacology
Volume5
Issue number3
DOIs
StatePublished - Sep 1 2010

Fingerprint

Cannabinoid Receptor CB2
HIV-1
Encephalitis
Virus Diseases
Brain
HLA-DQ Antigens
Endocannabinoids
Aptitude
Fas Ligand Protein
Putamen
Neuroaid
Blood-Brain Barrier
Neuroglia
Cognition
HIV Infections
Leukocytes
Spleen
Macrophages
Lymphocytes

Keywords

  • CB2R
  • HIV-1-associated neurocognitive disorders
  • human immunodeficiency virus
  • neuroinflammation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids. / Gorantla, Santhi; Makarov, Edward; Roy, Deepa; Finke-Dwyer, Jennifer; Murrin, L. Charles; Gendelman, Howard Eliot; Poluektova, Larisa Y.

In: Journal of Neuroimmune Pharmacology, Vol. 5, No. 3, 01.09.2010, p. 456-468.

Research output: Contribution to journalArticle

Gorantla, Santhi ; Makarov, Edward ; Roy, Deepa ; Finke-Dwyer, Jennifer ; Murrin, L. Charles ; Gendelman, Howard Eliot ; Poluektova, Larisa Y. / Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids. In: Journal of Neuroimmune Pharmacology. 2010 ; Vol. 5, No. 3. pp. 456-468.
@article{090a8b25b0d2459eb1e0f9d9cf1e770c,
title = "Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids",
abstract = "Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood-brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.",
keywords = "CB2R, HIV-1-associated neurocognitive disorders, human immunodeficiency virus, neuroinflammation",
author = "Santhi Gorantla and Edward Makarov and Deepa Roy and Jennifer Finke-Dwyer and Murrin, {L. Charles} and Gendelman, {Howard Eliot} and Poluektova, {Larisa Y}",
year = "2010",
month = "9",
day = "1",
doi = "10.1007/s11481-010-9225-8",
language = "English (US)",
volume = "5",
pages = "456--468",
journal = "Journal of NeuroImmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids

AU - Gorantla, Santhi

AU - Makarov, Edward

AU - Roy, Deepa

AU - Finke-Dwyer, Jennifer

AU - Murrin, L. Charles

AU - Gendelman, Howard Eliot

AU - Poluektova, Larisa Y

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood-brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.

AB - Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood-brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.

KW - CB2R

KW - HIV-1-associated neurocognitive disorders

KW - human immunodeficiency virus

KW - neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=77955981912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955981912&partnerID=8YFLogxK

U2 - 10.1007/s11481-010-9225-8

DO - 10.1007/s11481-010-9225-8

M3 - Article

C2 - 20549374

AN - SCOPUS:77955981912

VL - 5

SP - 456

EP - 468

JO - Journal of NeuroImmune Pharmacology

JF - Journal of NeuroImmune Pharmacology

SN - 1557-1890

IS - 3

ER -