Cytokine regulation of env gene expression of human endogenous retrovirus-R in human vascular endothelial cells

To determine whether human endogenous retroviruses are implicated in the pa thogenesis of inflammatory vascular diseases of unknown etiology, we examin ed mRNA expression of a human endogenous retrovirus, HERV-R, which has a lo ng open reading frame in the env region, in cultured human vascular endothe lial and smooth muscle cells stimulated in the presence of various cytokine s, mRNA of HERV-R was always evident in these cells but not in fibroblastic cells. Levels of expression in vascular endothelial cells were significant ly regulated by treatment with tumor necrosis factor-alpha, interleukin (IL )-1 alpha, and IL-1 beta as up-regulators and interferon-gamma as a down-re gulator. These observations are interpreted to mean that HERV-R expression may be up- or down-regulated at sites of inflammation in vessels in vivo an d hence may play a pathogenetic role in inflammatory vascular diseases in h umans, perhaps similar to endogenous retroviruses in mouse models of polyar teritis nodosa in humans. (C) 1999 Academic Press.