Involvement of the sphingomyelin pathway in autocrine tumor necrosis factor signaling for human immunodeficiency virus production in chronically infected HL-60 cells Journal Article
| Authors: | Rivas, C. I.; Golde, D. W.; Vera, J. C.; Kolesnick, R. N. |
| Article Title: | Involvement of the sphingomyelin pathway in autocrine tumor necrosis factor signaling for human immunodeficiency virus production in chronically infected HL-60 cells |
| 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. |
| Keywords: | signal transduction; human cell; dose response; tumor cells, cultured; enzyme activity; enzyme linked immunosorbent assay; leukemia, promyelocytic, acute; antibodies, monoclonal; regulatory mechanism; nf-kappa b; human immunodeficiency virus; sphingosine; phospholipase a2; hydrolysis; tumor necrosis factor; hiv-1; ceramide; sphingomyelin phosphodiesterase; sphingomyelin; cell strain hl 60; latent virus infection; sphingomyelins; virus transcription; phospholipase c; phospholipase d; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; antigen p24; phospholipases |
| Journal Title: | Blood |
| Volume: | 83 |
| Issue: | 8 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1994-04-15 |
| Start Page: | 2191 |
| End Page: | 2197 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8161785 |
| DOI: | 10.1182/blood.V83.8.2191.2191 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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