## 4 Discussion  
Until now, little is known about the molecular mechanisms and preconditions crucial for sensitivity or resistance towards diverse ROS types. Herein, we aimed to characterize further the different sensitivities of Jurkat and THP-1 cells towards the oxidants H\({}_{2}\)O\({}_{2}\) and HOCl. Generally, Jurkat cells were more sensitive to H\({}_{2}\)O\({}_{2}\) than THP-1, whereas the THP-1 cells were more sensitive to HOCl than Jurkat. Furthermore, the Jurkats had a more pronounced difference between IC20 concentrations of HOCl and H\({}_{2}\)O\({}_{2}\) than the THP-1 cells. Cytotoxic effects of ROS, such as H\({}_{2}\)O\({}_{2}\) and HOCl, can be caused by direct oxidation of cellular proteins, lipids, and nucleic acids [39], as well as through modification of signaling molecules inducing downstream apoptotic pathways [40, 41]. Regarding the mode of cell death, we showed that H\({}_{2}\)O\({}_{2}\) and HOCl-activated caspase 3 and 7 mediated apoptosis in both cell lines at different rates and to different extents. HOCl is known to react with superoxide anion to form the apoptosis-inducing hydroxyl radical [42]. Differences in apoptosis activation in different cell lines might be due to the divergent availability of superoxide anions mediated either through the formation by NADPH oxidases (NOX) or through scavenging by superoxide dismutase (SOD). Moreover, Jurkat and THP-1 had similar basal GSH/GSSG ratios, and both treatments disturbed the GSH/GSSG ratio in both cell lines. However, THP-1 had a more substantial increase in GSSG than Jurkat cells for both treatments, which was the reverse of GSH levels. In general, the GSH/GSSG ratio is regarded as a vital indicator of the cells' redox state [43, 44]. Detoxification of H\({}_{2}\)O\({}_{2}\) can be achieved via glutathione peroxidoxidases (GPx), catalyzing the oxidation of reduced glutathione (GSH) with H\({}_{2}\)O\({}_{2}\) to glutathione disulfide (GSSG) [45, 46]. Our findings that THP-1 cells show higher GSSG levels after H\({}_{2}\)O\({}_{2}\) exposure while being less susceptible to H\({}_{2}\)O\({}_{2}\)-induced toxicity indicate that this cell line uses the GPx-mediated ROS scavenging more effectively than Jurkat cells. In Jurkat cells, HO-1 and IL-8 protein knockdown augmented ROS-mediated toxicity stronger with HOCl treatment, whereas in THP-1 cells, the toxicity increase was more pronounced with H\({}_{2}\)O\({}_{2}\). A knockdown of catalase could only slightly augment ROS cytotoxicity in THP-1 cells. The enzyme heme oxygenase 1 (HO-1) was shown to have a cytoprotective effect by reducing oxidative stress and inflammation processes [47]. HO-1 mainly degrades free heme to iron (Fe), carbon monoxide (CO), and biliverdin [48]. The induction of HO-1, transcriptionally regulated by Nrf2, by oxidative stress is associated with ferritin induction [49]. Ferritin is an iron sequestrant associated with protection from oxidative stress-induced cellular damage [50, 51]. However, since free heme does not appear to occur in cell cultures, the mechanisms of its protective role in vitro remain unclear. The pro-inflammatory cytokine interleukin 8 (IL-8) is produced by several cell types, such as immune cells, fibroblasts, and endothelial cells, leading to neutrophil recruitment [52]. IL-8 secretion is known to be increased by oxidative stress [53] transcriptionally regulated by nuclear factor-kappaB (NF-kB) [54], but little is known about its detailed role in mediating resistance towards ROS-induced stress. A retrospective correlation analysis of oxidatively stressed cells of previous studies further revealed a good correlation of relative IL-8 concentrations with the release of IL-18 and IL-6 after plasma treatment (Supplementary Figure S1) which might serve as additional targets in future studies. Our data suggest that both HO-1 and IL-8 have important protective roles in mediating HOCl resistance in Jurkat, as well as H\({}_{2}\)O\({}_{2}\) resistance in THP-1 cells.