Jessica Wolf-Klenner

• The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) has been identified as the main receptor for oxidised low-density lipoprotein (oxLDL). It is most known for its involvement in atherosclerosis and its presence has been identified e.g. in immune and pulmonary cells. The gene of LOX-1 undergoes alternative splicing resulting in three different isoforms. However, the receptor has been identified in human cells and murine. The gene and the resulting isoforms differ between the two species. Therefore, it was aimed to analyse the expression of the LOX-1 isoforms in different human and murine cell samples as these splice variants might modulate differently. Hence, primers were established to analyse these isoforms and to determine the RNA expression in different cell types and under different stimulations. On that note, all three splice variants could be identified in human blood, immune cells, and pulmonary epithelial cells. However, the expression levels varied between the cell types and isoforms. Pulmonary epithelial cells had a higher expression than blood and immune cells. Monocytes showed with prolonged cultivation a decrease in LOX-1 expression. Additionally, the expression of LOX-1 was stimulated in blood-derived monocytes with oxLDL or infected with Staphylococcus aureus (S. aureus). These stimulation assays showed no significant increase in LOX-1 expression after 3h and 6h of stimulation. This showed that S. aureus might not lead to direct transcriptional regulation and that the oxLDL-dependent modulation of LOX-1 reported in literature might be a consequence of indirect signalling cascades in pro- inflammatory processes. For the murine LOX-1 isoforms only the main form could be identified in adult mice samples thereby confirming the results found in literature that the other two splice variants are only expressed during embryogenesis. However, we identified a total of 4 novel splice variants. One of these corresponds to the predicted variant X2 (NBCI database) whereas the other three have not yet been described in literature or any genomic database. The expression patterns of the newly identified variants and the main form also differed in the analysed cell samples. In conclusion, the LOX-1 isoform expression varies in different cell samples but cannot be directly stimulated at the transcriptional level in human monocytes with neither oxLDL nor S. aureus in the short term (3h or 6h). The murine LOX-1 seems to have splice variants only expressed in embryos, however, there seem to be more isoforms expressed than currently described in the literature in adult mouse samples which could have functional implications and relevance for the suitability between mouse models and human cells.