Role of DNA Methylation in Transcription of Human Endogenous Retrovirus in the Pathogenesis of Systemic Lupus Erythematosus

MAKIKO OKADA, HITOSHI OGASAWARA, HIROSHI KANEKO, TAKASHI HISHIKAWA, IWAO SEKIGAWA, HIROSHI HASHIMOTO, NAOKI MARUYAMA, YUTARO KANEKO, and NAOKI YAMAMOTO

ABSTRACT.

Objective. We recently reported that transcription of human endogenous retrovirus (HERV) clone 4-1-like sequences is increased in patients with systemic lupus erythematosus (SLE). We therefore investigated the role of DNA methylation in the transcription of this HERV.

Methods. The effect of a demethylating agent, 5-aza-deoxycytidine (5-aza C), on the transcription of HERV clone 4-1 in healthy individuals and patients with SLE was examined using reverse transcriptase-PCR and real-time quantitative PCR.

Results. 5-aza C increased clone 4-1-like messenger RNA in healthy controls, but not in patients with SLE.

Conclusion. Defects of methylation may contribute to the transcription of HERV in patients with SLE and this may be related to the pathogenesis of SLE. (J Rheumatol 2002;29:1678-82)

Key Indexing Terms:

HUMAN ENDOGENOUS RETROVIRUS
SYSTEMIC LUPUS ERYTHEMATOSUS
TRANSCRIPTION
METHYLATION

---

From the Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo; the Department of Medicine, Juntendo University Izu-Nagaoka Hospital, Shizuoka; the Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo; Ajinomoto, Co., Inc., Tokyo; and the Department of Microbiology, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan.

Supported by a High Technology Research Center grant from the Ministry of Education, Culture, and Sports of Japan, and a grant from the Imai Trust for AIDS Research.

M. Okada, PhD; H. Ogasawara, MD; H. Kaneko, MD; T. Hishikawa, MD; H. Hashimoto, MD, Professor, Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine; I. Sekigawa, MD, Associate Professor, Department of Medicine, Juntendo Izu-Nagaoka Hospital; N. Maruyama, MD, Director, Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology; Y. Kaneko, PhD, Ajinomoto Co., Inc.; N. Yamamoto, MD, Professor, Department of Microbiology, Tokyo Medical and Dental University School of Medicine.

Address reprint requests to Dr. I. Sekigawa, Department of Medicine, Juntendo University Izu-Nagaoka Hospital, 1129 Nagaoka, Izu-Nagaoka-cho, Tagata-gun, Shizuoka 410-2295, Japan. E-mail: naga-nai@lily.ocn.ne.jp

Submitted April 18, 2001; revision accepted February 27, 2002.

---