Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-Infected rhesus monkeys: Applications to HIV-induced central nervous system disease

Thomas E. Lane, Michael J. Buchmeier, Debbie D. Watry, Howard S. Fox

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalMolecular Medicine
Volume2
Issue number1
StatePublished - Dec 30 1996

Fingerprint

Simian Immunodeficiency Virus
Central Nervous System Diseases
Nitric Oxide Synthase Type II
Macaca mulatta
HIV
Cytokines
Haplorhini
Brain
Nitric Oxide
Microglia
HIV-1
Messenger RNA
Central Nervous System
Interleukin-1
Interferons
In Situ Hybridization
Motor Skills
Virus Diseases
Nitrites
Nervous System Diseases

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-Infected rhesus monkeys : Applications to HIV-induced central nervous system disease. / Lane, Thomas E.; Buchmeier, Michael J.; Watry, Debbie D.; Fox, Howard S.

In: Molecular Medicine, Vol. 2, No. 1, 30.12.1996, p. 27-37.

Research output: Contribution to journalArticle

@article{43c52db6c0844ac7b9aa7df7b9e6197b,
title = "Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-Infected rhesus monkeys: Applications to HIV-induced central nervous system disease",
abstract = "Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.",
author = "Lane, {Thomas E.} and Buchmeier, {Michael J.} and Watry, {Debbie D.} and Fox, {Howard S.}",
year = "1996",
month = "12",
day = "30",
language = "English (US)",
volume = "2",
pages = "27--37",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "1",

}

TY - JOUR

T1 - Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-Infected rhesus monkeys

T2 - Applications to HIV-induced central nervous system disease

AU - Lane, Thomas E.

AU - Buchmeier, Michael J.

AU - Watry, Debbie D.

AU - Fox, Howard S.

PY - 1996/12/30

Y1 - 1996/12/30

N2 - Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.

AB - Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.

UR - http://www.scopus.com/inward/record.url?scp=0029669179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029669179&partnerID=8YFLogxK

M3 - Article

C2 - 8900532

AN - SCOPUS:0029669179

VL - 2

SP - 27

EP - 37

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

IS - 1

ER -