Involvement of the sphingomyelin pathway in autocrine tumor necrosis factor signaling for human immunodeficiency virus production in chronically infected HL-60 cells.

Rivas CI, Golde DW, Vera JC, Kolesnick RN.

Abstract

Tumor necrosis factor (TNF) is a potent inducer of human immunodeficiency virus (HIV) proviral transcription and subsequent mature virus production. Recent investigations have shown that TNF can use a signal transduction pathway in HL-60 cells involving sphingomyelin hydrolysis to ceramide with subsequent stimulation of a ceramide-linked kinase. When sphingomyelinase was added exogenously to activate this cascade in HIV-1-infected HL-60 cells, it mimicked TNF-induced HIV production. Phospholipases A2, C, or D, which do not generate ceramide, had no effect; however, a synthetic ceramide analog added exogenously potently induced HIV production. In addition, anti-TNF antibodies blocked much of the effect of both sphingomyelinase and the synthetic ceramide analog on virus expression, suggesting that, although signaling is initiated through the sphingomyelin pathway, it is sustained by autocrine TNF synthesis. Thus, direct activation of the sphingomyelin pathway recapitulated the effect of TNF on both HIV and TNF production. These studies indicate that the sphingomyelin pathway is involved in TNF signaling for HIV production in chronically infected myeloid cells.

Más información

Título de la Revista: BLOOD
Volumen: 83
Número: 8
Editorial: AMER SOC HEMATOLOGY
Fecha de publicación: 1994
Página de inicio: 2191
Página final: 2197
Idioma: English
Notas: ISI