Effects of cyclopentenone prostaglandins on myeloid cells during early infection with HTLV-I. II. Regulation of synthesis of inducible p72 heat shock protein.
Differentiation of cells of myelomonocitic lineage influences both cellular permissivity to infection with human T-cell leukemia virus type I after cell-to-cell virus transmission and sensitivity to the antiproliferative effect of cyclopentenone prostaglandins (PG)A1 and PGJ2. Growth inhibition and control of infection were found to be associated with high intracellular levels of inducible p72 heat shock protein (HSP70). Pluripotent K562 cells produced higher HSP70 base-line levels than promyelocytic HL60 or monoblastoid U937 cells. Treatment with PGA1 and especially with PGJ2 enhanced the synthesis of HSP70 in all these cells. Notably, HSP70 accumulated in virus-exposed U937 cells (but not in K562 or HL60 cells). Because in lethally irradiated virus-donor cells HSP70 production was barely detectable, expression of this protein in cocultured U937 cells can be prevalently attributed to virus-recipient cells. Treatment with PGA1 and even more with PGJ2 remarkably enhanced the synthesis of HSP70 in virus-exposed U937 cells, thus resulting in persistently high levels of HSP70 protein in the cells. As shown previously, in U937 cells treatment with PGs was associated with reduced percentages of virus p19gag positive cells and enhanced specific lysis of virus-donor cells at early time points after cell-to-cell transmission. Because the HSP70 protein family is involved in the control of cell proliferation as well as in antigen processing function during the immune response to pathogens, it is possible that persistent high expression levels of HSP70 in PG-treated cells play a critical role in regulating both cell cycling and antiviral cellular responses.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
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Amici
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Bonmassar
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D'Onofrio
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology*; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2; C100573:prostaglandin A1