Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis.
Inflammatory cytokines and enzymes such as IL-1 and inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of AIDS dementia, a condition associated with infection of the CNS cells by the HIV-1. In this report, we investigated the expression of iNOS, IL-1, and caspase-1 (interleukin-1 converting enzyme) in HIV-1 encephalitis (HIVE) by immunocytochemistry and analyzed their expression with respect to HIV-1 infection and glial activation. In HIVE, all three molecules were expressed at high levels in areas of HIV-1 infection (microglial nodules with HIV-1 p24 immunoreactivity) and in areas of diffuse white matter gliosis. Expression was cell-type specific, with IL-1 and caspase-1 being expressed in macrophages and microglia, and iNOS in activated astrocytes. Multinucleated giant cells, a hallmark of virally infected cells, showed intense staining for both IL-1 and caspase-1, suggesting induction of these molecules by HIV-1. Double immunocytochemistry demonstrated a regional co-localization of astrocyte iNOS and microglial IL-1 and caspase-1. These results support the notion that autocrine and paracrine interactions between HIV-1 infected macrophages and microglia, activated microglia, and astrocytes lead to expression of proinflammatory and neurotoxic molecules. iNOS and caspase-1 may provide additional therapeutic targets for HIVE.
Department of Pathology (Neuropathology), F-717, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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Zhao
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Kim
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Morgello
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Lee
D015526:AIDS Dementia Complex / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020170:Caspase 1 / Q000096:biosynthesis*; D018792:Encephalitis, Viral / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II
D016655:HIV Core Protein p24; D015700:HIV Envelope Protein gp41; D007375:Interleukin-1; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020170:Caspase 1