title: Irradiation with UV-C inhibits TNF-α-dependent activation of the NF-κB pathway in a mechanism potentially mediated by reactive oxygen species.
abstract: Pathways depending on the NF-κB transcription factor are essential components of cellular response to stress. Plethora of stimuli modulating NF-κB includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affecting NF-κB remains relatively understudied. Here, we aim to characterize the influence of UV radiation on TNF-α-induced activity of the NF-κB pathway. We document inhibition of TNF-α-induced activation of NF-κB and subsequent suppression of NF-κB-regulated genes in cells exposed to UV-C several hours before TNF-α stimulation. Accumulation of ROS and subsequent activation of NRF2, p53, AP-1 and NF-κB-dependent pathways, with downstream activation of antioxidant mechanisms (e.g., SOD2 and HMOX1 expression), is observed in the UV-treated cells. Moreover, NF-κB inhibition is not observed if generation of UV-induced ROS is suppressed by chemical antioxidants. It is noteworthy that stimulation with TNF-α also generates a wave of ROS, which is suppressed in cells pre-treated by UV. We postulate that irradiation with UV-C activates antioxidant mechanisms, which in turn affect ROS-mediated activation of NF-κB by TNF-α. Considering a potential cross talk between p53 and NF-κB, we additionally compare observed effects in p53-proficient and p53-deficient cells and find the UV-mediated suppression of TNF-α-activated NF-κB in both types of cells.
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szoltysek
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Walaszczyk
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, Gliwice, Poland.|Systems Engineering Group, Silesian University of Technology, Akademicka 16, Gliwice, Poland.
authors.forename: Patryk
authors.initials: P
authors.lastname: Janus
authors.affiliation: Systems Engineering Group, Silesian University of Technology, Akademicka 16, Gliwice, Poland.|Departments of Statistics and Bioengineering, Rice University, 6100 Main Street, Houston, TX, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Kimmel
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D005786:Gene Expression Regulation / Q000528:radiation effects; D045325:HCT116 Cells; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D051547:Heme Oxygenase-1; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2; C498143:RELA protein, human; C495901:TP53 protein, human; C496541:HMOX1 protein, human