@misc{LiedtkeSchroederRoggenbucketal., author = {Liedtke, Victoria and Schr{\"o}der, Christian and Roggenbuck, Dirk and Weiss, Romano and Stohwasser, Ralf and Schierack, Peter and R{\"o}diger, Stefan and Schenk, Lysann}, title = {LEDGF/p75 is required for an efficient DNA damage response}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {11}, doi = {10.3390/ijms22115866}, pages = {1 -- 16}, language = {en} } @misc{LiedtkeRoseHiemannetal., author = {Liedtke, Victoria and Rose, Laura and Hiemann, Rico and Nasser, Abdullah and R{\"o}diger, Stefan and Bonaventura, Alena and Winkler, Laura and Sowa, Mandy and St{\"o}ckle, Michael and Schierack, Peter and Junker, Kerstin and Roggenbuck, Dirk}, title = {Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia—A Novel Diagnostic Approach with Therapeutic Consequence?}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {7}, issn = {1422-0067}, doi = {10.3390/ijms24076166}, abstract = {Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50\% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34\% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34\%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.}, language = {en} } @misc{WeissLiedtkeRoediger, author = {Weiss, Romano and Liedtke, Victoria and R{\"o}diger, Stefan}, title = {Cannabidiol does not cause DNA double-strand breaks in a human liver-derived cell model}, series = {Journal of cannabis research}, volume = {8}, journal = {Journal of cannabis research}, number = {1}, publisher = {Springer Science and Business Media LLC}, issn = {2522-5782}, doi = {10.1186/s42238-025-00365-w}, pages = {1 -- 15}, abstract = {Background Cannabidiol (CBD) is a non-psychoactive cannabinoid with potential therapeutic applications, including anti-inflammatory, analgesic, and anticancer effects. However, experts raised concerns about its potential to induce DNA damage and chromosomal aberrations at low concentrations. Notably, these studies used liver cell lines, which may not fully reflect the metabolic processing of CBD, potentially limiting the generalizability of their findings. This study investigated the short time effects of CBD on DNA double-strand breaks (DSBs) and proliferation in the human liver-derived cell line HepG2. Methods HepG2 cells were treated with CBD (5 - 50 , 3 - 72h incubation). To investigate potential imbalances in the expression of cannabinoid receptors 1 and 2 (CB1 / CB2) within HepG2 cells, we examined their expression using Western blot analysis. We hypothesized that such an imbalance could be associated with pathogenic processes. Double-strand breaks were then detected (5 Etoposide (ETP) served as positive control) via indirect immunofluorescence analysis using H2AX and 53BP1 antibodies, followed by quantification of DSB foci. Results Expression of CB2 but not CB1 was downregulated by 30 \% in HepG2 cells after exposure to 5 CBD (24h incubation; 0.05) and 70 \% downregulated after exposure to 50 CBD (24h incubation; 0.01). This effect was dose-dependent. Whilst ETP induced dose dependent DSBs, we could not confirm findings by others that CBD significantly increases the number of H2AX and 53BP1 foci between 5 and 50 (3h incubation; 0.05). Conclusion In our model, CBD stimulated the cells, as confirmed by modulation of CB2 expression as well as changes in intracellular cAMP. Our results show that CBD in ranges between 5 to 50 does not significantly increase the amount of DNA double strand breaks in HepG2 cells compared to the control. However, we did observe a significant reduction in cell proliferation and a significant increase in intracellular cAMP levels following CBD treatment.}, language = {en} }