Possible role of DNA hypomethylation in the induction of SLE: relationship to the transcription of human endogenous retroviruses.
OBJECTIVE
We investigated the contribution of DNA methyltransferase activity to the transcription of human endogenous retroviruses (HERV), which have been reported to be a plausible causative agent for systemic lupus erythematosus (SLE).


METHODS
The reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative-PCR (RQ-PCR) were used.


RESULTS
Our results indicated that treatment with 5-aza-deoxycytidine (5-aza C), a demethylating agent, increased the transcription of messenger RNA (mRNA) for HERV clone 4-1 and decreased mRNA for DNA methyltransferase-1 (DNMT-1; methylation-regulating enzyme) in peripheral blood mononuclear cells (PBMC) from normal individuals. Also, transcription of DNMT-1 mRNA in PBMC from patients with SLE was lower than in cells from normal controls.


CONCLUSIONS
DNA hypomethylation seems to play a significant role in the transcription of HERV clone 4-1 and may be related to the pathogenesis of SLE.
Ogasawara
H
H
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Okada
M
M
Kaneko
H
H
Hishikawa
T
T
Sekigawa
I
I
Hashimoto
H
H
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D019175:DNA Methylation; D004279:DNA, Viral / Q000032:analysis; D020077:Endogenous Retroviruses / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D004279:DNA, Viral; D012333:RNA, Messenger