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

1. The role of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the mechanism of cell death induced by the human immunodeficiency virus type 1 (HIV-1) recombinant coat glycoprotein, gp120 IIIB, has been studied in the human CHP 100 neuroblastoma cell line maintained in culture. 2. Death of neuroblastoma cells typically elicited by 10 pM gp120 or by human recombinant IL-1β (10 ng ml -1) has been minimized by the antagonist of IL-1 receptor, i.e. IL-1 ra (0.5 and 50 ng ml -1, respectively), an endogenous molecule that antagonizes most of the biological actions of IL-1β, or by an antibody (5 and 50 ng ml -1) which blocks the human IL-1 receptor type I (IL-1RI). 3. ELISA experiments have established that gp120 enhances immunoreactive IL-1β levels in the culture medium and this is prevented by exposure to the IL-1 converting enzyme (ICE) inhibitor t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone [Boc-Asp(OBz1)-CMK] used at a concentration (2.5 μM) 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 μM), a second inhibitor of ICE, supporting the concept that the viral protein stimulates the conversion of the 31 kDa pro-IL-1β in to the 17 kDa mature cytokine which is then secreted to cause death. 5. In conclusion, our present data demonstrate that gpl20 stimulates the secretion of IL-1β which then triggers CHP100 neuroblastoma cell death via stimulation of IL-1 receptor type I.