Short communication Caspase-1 inhibitors abolish deleterious enhancement of COX- 2 expression induced by HIV-1 gp120 in human neuroblastoma cells M.T. Corasaniti a, *, C. Bellizzi a,b , R. Russo a , C. Colica a,b , D. Amantea b , G. Di Renzo a a Department of Pharmacobiological Sciences, University ‘Magna Graecia’ of Catanzaro, Faculty of Pharmacy, C/o Complesso ‘Ninı ` Barbieri’, 88021 Roccelletta di Borgia (CZ), Catanzaro, Italy b Department of Pharmacobiology, University of Calabria, Cosenza, Italy Abstract 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-1b. In fact, here we show that acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and t -butoxycarbo- nyl-L-aspartic acid benzyl ester-chloromethylketone (Boc-Asp-(OBzl)-CMK), two inhibitors of Interleukin-1 Convert- ing 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-1b is the signal through which gp120 elevates COX-2 expression and the latter is strongly implicated in the mechanisms underlying cytotoxicity. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: HIV-1 gp120; COX-2; IL-1b; Caspase-1; NS-398; Ac-YVAD-CMK; Boc-Asp-(OBzl)-CMK; Cell death; Neuroblastoma cells 1. Introduction The HIV-1 coat glycoprotein, gp120, seems to play a crucial role in the progression of neurolo- gical complications and brain damage which afflict a large proportion of patients suffering from AIDS (Kaul et al., 2001). In the past few years employ- ment of the human CHP100 neuroblastoma cell line has been shown to provide an useful in vitro model to elucidate the mechanisms underlying gp120-neurotoxicity (Corasaniti et al., 1995, 1996, 1998, 2001a; Catani et al., 2000). Interaction of gp120 with NMDA (Corasaniti et al., 1995) and chemokine receptors (Catani et al., 2000), conse- quent increase of intracellular Ca 2 concentration * Corresponding author. Tel.:  /39-961-391-157; fax:  /39- 961-391-490 E-mail address: mtcorasa@unicz.it (M.T. Corasaniti). Toxicology Letters 139 (2003) 213  /219 www.elsevier.com/locate/toxlet 0378-4274/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0378-4274(02)00436-8