HIV-1 coat protein gp120 stimulates interleukin-1β secretion from human neuroblastoma cells:: evidence for a role in the mechanism of cell death

1 The role of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) in the mechanism of cell death induced by the human immunodeficiency virus type I (HIV-1) recombinant coat glycoprotein, gp120 IIIB, has been studied in the human CHP100 neuroblastoma cell line maintained in culture. 2 Death of neuroblastoma cells typically elicited by 10 pm gp120 or by human recombinant IL-1 beta (10 ng ml(-1)) has been minimized by the antagonist of IL-I receptor, i.e. IL-1ra (0.5 and 50 ng ml(-1), respectively), an endogenous molecule that antagonizes most of the biological actions of IL-1 beta, or by an antibody (5 and 50 ng ml(-1)) which blocks the human IL-I receptor type I (IL-1RI). 3 ELISA experiments have established that gp120 enhances immunoreactive IL-1 beta levels in the culture medium and this is prevented by exposure to the IL-I converting enzyme (ICE) inhibitor t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone [Boc-Asp(OBzl)-CMK] used at a concentration (2.5 mum) which significantly (P <0.001) reduces cell death. 4 Death of CHP100 cells induced by gp120 is also prevented by acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK; 10-100 mum), a second inhibitor of ICE, supporting the concept that the viral protein stimulates the conversion of the 31 kDa pro-IL-1 beta in to the 17 kDa mature cytokine which is then secreted to cause death. 5 In conclusion, our present data demonstrate that gp120 stimulates the secretion of IL-1 beta which then triggers CHP100 neuroblastoma cell death via stimulation of IL-I receptor type 1.