Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation

Ultraviolet radiation is a pathogenic factor in various diseases, e.g., aut oimmune disorders such as lupus erythematosus. On the other hand, endogenou s retroviruses are discussed as etiologic agents in lupus erythematosus. Th erefore, we investigated the influence of ultraviolet irradiation on expres sion of human endogenous retroviral sequences and human endogenous retrovir al sequence promoter-driven transcription of cellular genes using human epi dermal keratinocytes as a model system. First, conserved sequences of endog enous retroviral pot genes were amplified from cellular mRNA by reverse tra nscriptase polymerase chain reaction with degenerate oligonucleotide primer s. Polymerase chain reaction products were hybridized in a reverse dot blot hybridization assay to a representative number of distinct cloned human en dogenous retroviral pol fragments. Using this method, we could show that ir radiation with 30 mJ per cm(2) ultraviolet B activates transcription of var ious endogenous retroviral pol sequences in primary epidermal keratinocytes as well as in a spontaneously immortalized keratinocyte cell line (HaCaT), Interestingly, some of these sequences were found to be closely related to pol sequences of human endogenous retroviral sequences which have been sho wn to be expressed in autoimmune patients. Analysis of human endogenous ret roviral pol expression in vivo using skin biopsies of lupus erythematosus p atients revealed similar activation patterns. In a second approach, ultravi olet B- induced chimeric transcripts were isolated which are initiated by h uman endogenous retroviral promoters and proceed into cellular sequences us ing a newly established modified differential display polymerase chain reac tion technique. The activation of human endogenous retroviral sequence tran scription by ultraviolet B may contribute to the pathogenesis of lupus eryt hematosus, where inappropriate antigenic presentation of ultraviolet B-indu ced viral and cellular proteins could stimulate autoantibody production.