Journal
TOXICOLOGY LETTERS
Volume 139, Issue 2-3, Pages 213-219Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(02)00436-8
Keywords
HIV-1 gp120; COX-2; IL-1 beta; caspase-1; NS-398; Ac-YVAD-CMK; Boc-Asp-(OBzl)-CMK; cell death; neuroblastoma cells
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The human CHP100 neuroblastoma cell line has been shown to provide an useful in vitro model to elucidate the mechanisms underlying HIV-1 gp120 neurotoxicity. Here we report western blotting evidence demonstrating that exposure to a cytotoxic concentration of the viral coat protein up-regulates expression of the inducible isoform of cyclooxygenase (COX-2) in neuroblastoma cells and this seems to be due to the previously observed increase in secreted IL-1beta. In fact, here we show that acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone (Boc-Asp-(OBzl)-CMK), two inhibitors of Interleukin-1 Converting Enzyme (ICE; also referred to as caspase-1), abolish COX-2 expression enhanced by gp120 and consequent cell death. In addition, NS-398, a selective inhibitor of COX-2 activity, affords neuroprotection strengthening the role of COX-2 in the mechanisms of death. In conclusion, the present data support the notion that IL-1beta is the signal through which gp120 elevates COX-2 expression and the latter is strongly implicated in the mechanisms underlying cytotoxicity. beta 2002 Elsevier Science Ireland Ltd. All rights reserved.
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