[HTML][HTML] Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-infected rhesus monkeys: applications to HIV-induced central …
Molecular Medicine, 1996•Springer
Background Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The
mechanism (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 …
system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The
mechanism (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 …
Background
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The mechanism(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 DL-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.
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