Irradiation with<scp>UV</scp>‐C inhibits<scp>TNF</scp>‐α‐dependent activation of the<scp>NF</scp>‐κB pathway in a mechanism potentially mediated by reactive oxygen species

Szołtysek, Katarzyna; Walaszczyk, Anna; Janus, Patryk; Kimmel, Marek; Widłak, Piotr

doi:10.1111/gtc.12455

Cited by 13 publications

(13 citation statements)

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“…An antagonistic effect of p53 and NF-κB is apparently not limited to cells stimulated by ionizing radiation. We have previously reported the enhanced expression of typical NF-κB-dependent genes (including CXCL8 , NFKB1 , REL, and TNFAIP3 ) in TNFα-stimulated p53-null HCT116 cells [ 32 ]. Moreover, we took advantage of the U2-OS experimental model and found 39 genes upregulated after 30 min of stimulation with TNFα cytokine, whose expression was inhibited in cells with downregulated RELA .…”

Section: Discussionmentioning

confidence: 99%

RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation

et al. 2018

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BackgroundThe cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gene targets. Here we looked for novel genes potentially (co)regulated by p53 and NF-κB using integrative genomics screening in human osteosarcoma U2-OS cells irradiated with a high dose (4 and 10 Gy). Radiation-induced expression in cells with silenced TP53 or RELA (coding the p65 NF-κB subunit) genes was analyzed by RNA-Seq while radiation-enhanced binding of p53 and RelA in putative regulatory regions was analyzed by ChIP-Seq, then selected candidates were validated by qPCR.ResultsWe identified a subset of radiation-modulated genes whose expression was affected by silencing of both TP53 and RELA, and a subset of radiation-upregulated genes where radiation stimulated binding of both p53 and RelA. For three genes, namely IL4I1, SERPINE1, and CDKN1A, an antagonistic effect of the TP53 and RELA silencing was consistent with radiation-enhanced binding of both p53 and RelA. This suggested the possibility of a direct antagonistic (co)regulation by both factors: activation by NF-κB and inhibition by p53 of IL4I1, and activation by p53 and inhibition by NF-κB of CDKN1A and SERPINE1. On the other hand, radiation-enhanced binding of both p53 and RelA was observed in a putative regulatory region of the RRAD gene whose expression was downregulated both by TP53 and RELA silencing, which suggested a possibility of direct (co)activation by both factors.ConclusionsFour new candidates for genes directly co-regulated by NF-κB and p53 were revealed.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5211-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation

et al. 2018

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“…Although UVC is regarded as a poor activator of the Nrf2 response in some cell types [59], exposure of HCT116 colon carcinoma cells to UVC (20 J/m 2 ) did cause a marked activation of Nrf2 and transcription of its downstream target heme oxygenase-1 (HO-1), likely by promoting the generation of ROS [60]. This pathway might thus play a role in the cellular response to UVC in some circumstances.…”

Section: P53 Is An Early Stress Level-dependent Rheostat In the Respomentioning

confidence: 99%

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Murray

Mirzayans

2020

IJMS

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Chemotherapy is intended to induce cancer cell death through apoptosis and other avenues. Unfortunately, as discussed in this article, moderate doses of genotoxic drugs such as cisplatin typical of those achieved in the clinic often invoke a cytostatic/dormancy rather than cytotoxic/apoptosis response in solid tumour-derived cell lines. This is commonly manifested by an extended apoptotic threshold, with extensive apoptosis only being seen after very high/supralethal doses of such agents. The dormancy response can be associated with senescence-like features, polyploidy and/or multinucleation, depending in part on the p53 status of the cells. In most solid tumour-derived cells, dormancy represents a long-term survival mechanism, ultimately contributing to disease recurrence. This review highlights the nonlinearity of key aspects of the molecular and cellular responses to bulky DNA lesions in human cells treated with chemotherapeutic drugs (e.g., cisplatin) or ultraviolet light-C (a widely used tool for unraveling details of the DNA damage-response) as a function of the level of genotoxic stress. Such data highlight the growing realization that targeting dormant cancer cells, which frequently emerge following conventional anticancer treatments, may represent a novel strategy to prevent or, at least, significantly suppress cancer recurrence.

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“…These processes might seem unlikely to regulate both molecules as they are localized in different cellular compartments. As reported previously, ROS produced by NADPH oxidases can act as a second messenger for regulating the NF- κ B activation [ 25 , 26 ]. ROS exerts a dual role in cell growth: cellular senescence or apoptosis or antiapoptosis-dependent NF- κ B activity [ 21 , 22 , 27 ].…”

Section: Discussionmentioning

confidence: 88%

Using ROS as a Second Messenger, NADPH Oxidase 2 Mediates Macrophage Senescence via Interaction with NF‐κB during Pseudomonas aeruginosa Infection

Luo

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

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Pseudomonas aeruginosa (PA) is one of the most prevalent pathogens that cause nosocomial infection in critical patients. However, the mechanisms underlying macrophage growth status and functional changes during PA infection are yet unknown. In the present study, NADPH oxidase, gp91phox (NOX2) mediated macrophage to senescence in a PAO1 colony-dependent manner. gp91phox might regulate the senescence process through mutual interaction with the NF-κB pathway. During infection, the overexpression or downregulation of gp91phox in macrophage could affect the nuclear activity of NF-κB p65, while the downregulation of NF-κB p65 led to a suppressed expression of gp91phox. Reactive oxygen species (ROS) served as the second messenger between both molecules as the ROS inhibitor, N-acetylcysteine (NAC), could partially restore these changes. Consequently, the level of ROS and inflammatory cytokines, including IL-6 and TNFα, elevated during PAO1 infection, and their production altered as a result of the genetic manipulation of gp91phox and NF-κB p65, as well as NAC treatment. Also, the senescent phenotypes, SA-β-gal staining and p16ink4a, changed after genetic manipulation with gp91phox and NF-κB p65 and NAC treatment. The capacity of phagocytosis in macrophages was decreased during senescence. In conclusion, PA directs the macrophage towards senescence, and senescent macrophages exhibit a decreased ability of phagocytosis. This process of senescence was regulated by the interactions between NADPH oxidase gp91phox and NF-κB p65 via ROS as a second messenger.

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Irradiation withUV‐C inhibitsTNF‐α‐dependent activation of theNF‐κB pathway in a mechanism potentially mediated by reactive oxygen species

Cited by 13 publications

References 55 publications

RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation

RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Using ROS as a Second Messenger, NADPH Oxidase 2 Mediates Macrophage Senescence via Interaction with NF‐κB during Pseudomonas aeruginosa Infection

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