Elsevier

Clinical Immunology

Volume 93, Issue 1, October 1999, Pages 75-80
Clinical Immunology

Regular Article
Cytokine Regulation of env Gene Expression of Human Endogenous Retrovirus-R in Human Vascular Endothelial Cells

https://doi.org/10.1006/clim.1999.4762Get rights and content

Abstract

To determine whether human endogenous retroviruses are implicated in the pathogenesis of inflammatory vascular diseases of unknown etiology, we examined mRNA expression of a human endogenous retrovirus, HERV-R, which has a long open reading frame in the env region, in cultured human vascular endothelial and smooth muscle cells stimulated in the presence of various cytokines. mRNA of HERV-R was always evident in these cells but not in fibroblastic cells. Levels of expression in vascular endothelial cells were significantly regulated by treatment with tumor necrosis factor-α, interleukin (IL)-1α, and IL-1β as up-regulators and interferon-γ as a down-regulator. These observations are interpreted to mean that HERV-R expression may be up- or down-regulated at sites of inflammation in vessels in vivo and hence may play a pathogenetic role in inflammatory vascular diseases in humans, perhaps similar to endogenous retroviruses in mouse models of polyarteritis nodosa in humans.

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      HERV gene expression is principally regulated by their individual LTRs. Cytokines such as TNF-α are known to regulate HERV expression in a temporal and tissue-specific fashion [89,90]. Although most HERV integration events are ancient, there are human-specific integrations for HERV-K (HML-2, 113 and 115) that are relatively new (400,000–250,000 years ago) and the full-length provirus and pre-integration site alleles are present in the human population [32].

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    This work was supported in part by grants from the Ministries of Health and Welfare, and Education, Culture, Science, and Sports of Japan.

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    To whom correspondence and reprints should be addressed. Fax: +81(11)706-7825. E-mail: [email protected].

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