[Expression of human endogenous retroviruses in rheumatoid arthritis]

The genomes of all organisms, from yeast to humans, contain thousands of endogenous retroviruses (ERVs) and ERVs are transmitted vertically through germ cells as provirus. In recent studies, it has been reported that some ERVs have important immunologic effects and are associated with autoimmune diseases in several animals. However, despite many years of investigation in human, physiological or pathological roles for ERVs remain unknown. In this study we examined whether the pathogenesis of rheumatoid arthritis (RA) was associated with human ERVs; ERV3 and lambda 4-1, which retain open reading frames (ORF) and could make proteins. We demonstrated that ERV3 and lambda 4-1 were expressed on synoviocytes and peripheral blood mononuclear cells (PBMCs) in RA patients by Northern blot analysis. But the expression was indeed heterogenous: RA patients showed various expression levels of ERV3 and lambda 4-1, which were independent of clinical activities and kinds of used drugs. mRNAs of ERV3 and lambda 4-1 were also expressed in PBMCs of healthy volunteers. We detected a 4.2 kb transcript of lambda 4-1 in synoviocytes and PBMCs which was not expressed in placentas, suggesting a unique protein might be produced in synoviocytes and PBMCs compared to placentas. In order to examine regulatory mechanisms for expression of human ERVs, we treated cultured synoviocytes and human kidney endothelial cells (hKEC) with various cytokines. By interleukin-1 beta (IL-1 beta) treatment, ERV3 expression in synoviocytes was not altered, but that in hKEC increased and correlated with IL-6 expression. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenesis of RA, the possibility still exists that some of many ERVs, which are integrated into human genomes, may have causative roles in RA.