HIV-1 envelope glycoprotein 120 regulates brain IL-1beta system and TNF-alpha mRNAs in vivo.
Human immunodeficiency virus type I (HIV-1)-derived envelope glycoprotein 120 (gp120) is proposed to play an important role in HIV-1 neuropathology. Gp120 may act through mediators including proinflammatory cytokines. Here, we investigated the regulation of the IL-1beta system [IL-1beta, IL-1 receptor type I (IL-1RI), IL-1 receptor antagonist (IL-1Ra)], TNF-alpha and TGF-alpha mRNAs in the rat central nervous system (CNS) in response to the constant intracerebroventricular (ICV) microinfusion of HIV-1 gp120 for 72 h and 144 h. The results show that gp120: (1) increased IL-1beta and IL-1Ra mRNAs levels in the same samples from the cerebellum, hypothalamus and midbrain, with the largest increase in the hypothalamus; (2) induced profiles of IL-1beta mRNA and IL-1Ra mRNA that were highly intercorrelated; (3) increased the hypothalamic TNF-alpha mRNA levels; and (4) did not affect the IL-1RI mRNA and TGF-alpha mRNA levels in any brain region. A dysregulation in the IL-1beta/IL-1Ra CNS balance and a mutual induction and synergistic activity of IL-1beta and TNF-alpha could result in a deleterious amplification cycle of cellular activation and cytotoxicity with implications to HIV-1-associated encephalitis, encephalopathy, and neurological manifestations.
Ilyin
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Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark 19716-2590, USA.
Plata-Salamán
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D000818:Animals; D001921:Brain / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha