Inhibition of 6-formylindolo[3,2-b]carbazole metabolism sensitizes keratinocytes to UVA-induced apoptosis: Implications for vemurafenib-induced phototoxicity

Rolfes, Katharina M.; Sondermann, Natalie C.; Vogeley, Christian; Dairou, Julien; Gilardino, Viola; Wirth, Ragnhild; Meller, Stephan; Homey, Bernhard; Krutmann, Jean; Lang, Dieter; Nakamura, Minoru; Haarmann‐Stemmann, Thomas

doi:10.1016/j.redox.2021.102110

Cited by 7 publications

(2 citation statements)

References 68 publications

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“…On the other hand, strong or longer lasting phototoxic stress may cause ROS-mediated cytotoxicity and necrotic cell death not only in normal epidermal cells but also in initiated keratinocytes and malignant cells. Interestingly, several UVB radiation-induced photoproducts of tryptophan, including NFK and FICZ, have been identified as potent UVA photosensitizers ( 110 , 163 , 164 ), and a combinatorial treatment with FICZ and UVA radiation was proposed as a novel therapeutic approach for skin cancer ( 165 ). Notably, other investigators regard the oxidative stress resulting from the FICZ/UVA exposure and the associated inhibition of DNA repair enzymes as a pro-carcinogenic event ( 166 ).…”

Section: Co-carcinogenicity Of Uv Radiation and Pahs?mentioning

confidence: 99%

The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin

et al. 2022

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Cutaneous squamous cell carcinoma (SCC) is one of the most frequent malignancies in humans and academia as well as public authorities expect a further increase of its incidence in the next years. The major risk factor for the development of SCC of the general population is the repeated and unprotected exposure to ultraviolet (UV) radiation. Another important risk factor, in particular with regards to occupational settings, is the chronic exposure to polycyclic aromatic hydrocarbons (PAH) which are formed during incomplete combustion of organic material and thus can be found in coal tar, creosote, bitumen and related working materials. Importantly, both exposomal factors unleash their carcinogenic potential, at least to some extent, by activating the aryl hydrocarbon receptor (AHR). The AHR is a ligand-dependent transcription factor and key regulator in xenobiotic metabolism and immunity. The AHR is expressed in all cutaneous cell-types investigated so far and maintains skin integrity. We and others have reported that in response to a chronic exposure to environmental stressors, in particular UV radiation and PAHs, an activation of AHR and downstream signaling pathways critically contributes to the development of SCC. Here, we summarize the current knowledge about AHR’s role in skin carcinogenesis and focus on its impact on defense mechanisms, such as DNA repair, apoptosis and anti-tumor immune responses. In addition, we discuss the possible consequences of a simultaneous exposure to different AHR-stimulating environmental factors for the development of cutaneous SCC.

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Section: Co-carcinogenicity Of Uv Radiation and Pahs?mentioning

confidence: 99%

The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin

et al. 2022

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“…IL-22 can be regulated by positive inducers including IL-6, IL-21, IL-23, IL-1β, IL-7, AHR, Notch and negative controllers such as TGF-β, IRF-4, IL-27, ICOS, and c-Maf ( Figure 2 ). Interestingly, ultraviolet B irradiation of keratinocytes increased the productions of both AHR ligand ( 69 , 70 ) and IL-22R1 ( 71 ), amplifying the roles of Th22 cells and IL-22 ( Figure 1 ). Soluble IL-22 binding proteins (IL-22BP, or IL-22R2) serve as its natural inhibitor.…”

Section: Biological Activities Of Th22 Cells and Il-22 In The Skinmentioning

confidence: 99%

The Role of T Helper 22 Cells in Dermatological Disorders

Pan

Wang

et al. 2022

Front. Immunol.

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T helper 22 (Th22) cells are a newly identified subset of CD4+ T cells that secrete the effector cytokine interleukin 22 (IL-22) upon specific antigen stimulation, barely with IFN-γ or IL-17. Increasing studies have demonstrated that Th22 cells and IL-22 play essential roles in skin barrier defense and skin disease pathogenesis since the IL-22 receptor is widely expressed in the skin, especially in keratinocytes. Herein, we reviewed the characterization, differentiation, and biological activities of Th22 cells and elucidated their roles in skin health and disease. We mainly focused on the intricate crosstalk between Th22 cells and keratinocytes and provided potential therapeutic strategies targeting the Th22/IL-22 signaling pathway.

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Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway

Sondermann

Faßbender

Hartung

et al. 2023

Biochemical Pharmacology

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Inhibition of 6-formylindolo[3,2-b]carbazole metabolism sensitizes keratinocytes to UVA-induced apoptosis: Implications for vemurafenib-induced phototoxicity

Cited by 7 publications

References 68 publications

The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin

The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin

The Role of T Helper 22 Cells in Dermatological Disorders

Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway

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