[Effects of interferon on the expressions of TRAIL and other apoptosis- inducing genes in peripheral blood mononuclear cells from polycythemia rubra vera].
OBJECTIVE
To investigate the effects of interferon (IFN) on the natural killer (NK) cytotoxicity and the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and other apoptosis-inducing genes in peripheral blood mononuclear cells (PBMNC) from polycythemia rubra vera (PV).


METHODS
PBMNC were collected from 12 PV patients. The NK cytotoxicity was assessed by lactate dehydrogenase release assay and lytic units (LU) were calculated based on specific lysis. The TRAIL mRNA and other apoptosis-inducing genes were determined by RNase protection assay.


RESULTS
The NK cytotoxicity of untreated PBMNC from PV was (152.0 +/- 146.6) LU. And of IFNalpha1b- and IFNalpha2b-treated PBMNC were up to (250.9 +/- 197.4) LU and (355.9 +/- 249.9) LU, respectively (P < 0.05 and P < 0.01, respectively). The expression of TRAIL mRNA was upregulated in IFNalpha1b and IFNalpha2b stimulated-PBMNC. Up-regulation of mRNA levels of FLICE, DR3, DR4 and TNFRp55 genes was observed in PBMNC after stimulated with IFNalpha, which also induced the mRNA expressions of FasL, Fas, TRADD and RIP. To explore the role of TRAIL in IFNalpha-augmented NK cytotoxicity, neutralizing assay was used and the results showed that IFNalpha-augmented NK activity could be blocked partially by peptides DR4-Fc and DR5-Fc.


CONCLUSIONS
IFNalpha induced/upregulated the expression of TRAIL and other apoptosis-inducing genes in PBMNC from PV patients, which partially contribute to the IFNalpha-augmented NK cytotoxicity augmentation. This may be one of the mechanisms of IFNalpha therapy for PV.
Liu
Yan-fang
YF
Department of Hematology, First Teaching Hospital of Zhengzhou University, Institute of Clinic Medical Research of University in Henan Province, Zhengzhou 450052, China.
Chen
Sheng-mei
SM
Sun
Hui
H
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000097:blood* / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D016898:Interferon-alpha; D053221:TNF-Related Apoptosis-Inducing Ligand