Autocrine loop of tumor necrosis factor induced by interferon-alpha in tumor cells from hairy cell leukemia.
Interferon-alpha (IFN-alpha) is successfully used in the therapy of hairy cell leukemia (HCL). We previously reported that IFN-alpha administered to HCL patients stimulated the levels of tumor necrosis factor (TNF) receptors on hairy cells. Here, we investigated the interactions between IFN-alpha and TNF, using the HCL cell line Eskol as a model. We showed that increased levels of TNF receptors (TNFR) induced by IFN-alpha treatment were associated with stimulation of high M(r) TNFR. Low M(r) TNFR were not detected on Eskol cells or hairy cells, either before or after IFN-alpha treatment. Furthermore, the expression of TNF mRNA increased in Eskol cells treated with IFN-alpha for 1-4 h as compared to control cells. In vivo experiments showed that IFN-alpha given to HCL patients induced both TNF mRNA expression in hairy cells and secretion of active TNF protein in patients' serum. These results provide evidence that IFN-alpha may induce an autocrine loop of TNF in HCL.
Unité de Recherches Interférons et Cytokines, INSERM U 365, Institut Curie, Paris, France.
N
N
Romquin
C
C
Billard
D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D016898:Interferon-alpha; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha