In vitro evidence for a dual role of tumor necrosis factor-? in human immunodeficiency virus type 1 encephalopathy
| Autor: | Diane E. Griffin, Jia Min Zhou, Elizabeth A. Milward, Heather Patton, Susan G. Wilt, Ray Rusten, Michael J. O'Connor, Kunihiko Nagasato, Monique Dubois-Dalcq |
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| Rok vydání: | 1995 |
| Předmět: |
AIDS Dementia Complex
medicine.medical_treatment Molecular Sequence Data HIV Core Protein p24 Apoptosis Biology Virus Replication Polymerase Chain Reaction Antibodies Receptors Tumor Necrosis Factor Myelin Antigens CD medicine Humans RNA Messenger Pentoxifylline Cells Cultured Base Sequence Microglia Tumor Necrosis Factor-alpha Recombinant Proteins Oligodendrocyte Oligodendroglia Microglial cell activation medicine.anatomical_structure Cytokine Neurology Viral replication Receptors Tumor Necrosis Factor Type I Immunology HIV-1 Cancer research Tumor necrosis factor alpha Neurology (clinical) |
| Zdroj: | Annals of Neurology. 37:381-394 |
| ISSN: | 1531-8249 0364-5134 |
| Popis: | Microglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)-alpha message have been observed in the brains of some human immunodeficiency virus type 1 (HIV-1)-infected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF-alpha in HIV-1 encephalopathy. Human microglia synthesize TNF-alpha message and protein in vitro. When these cells were infected with HIV-1 JrFL and maintained in the presence of TNF-alpha antibodies, soluble TNF-alpha receptors, or the TNF-alpha inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF-R1, which has been implicated in cytotoxicity, and TNF-R2. While TNF-alpha may enhance HIV-1 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF-alpha causes oligodendrocyte death in a dose-dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF-alpha inhibitors. We propose that TNF-alpha plays a dual role in HIV-1 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF-alpha inhibitors may alleviate some of the neurological manifestations of acquired immunodeficiency syndrome. |
| Databáze: | OpenAIRE |
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