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ORIGINAL RESEARCH article

Front. Med.
Sec. Dermatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1483208
This article is part of the Research Topic Advancements in Human Skin Photobiology: Exploring the Intricate Relationship between Human Skin and Light View all 3 articles

New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in Ultraviolet-induced cutaneous carcinogenesis

Provisionally accepted
Aleksandra Lesiak Aleksandra Lesiak Karolina Wodz Karolina Wodz Justyna Ceryn Justyna Ceryn Dorota Sobolewska -Sztychny Dorota Sobolewska -Sztychny Igor Bednarski Igor Bednarski Janusz Piekarski Janusz Piekarski Marta Pabianek Marta Pabianek Dariusz Nejc Dariusz Nejc Izabela Dróżdż Izabela Dróżdż Joanna Narbutt Joanna Narbutt Marcin Noweta Marcin Noweta Magdalena Ciazynska Magdalena Ciazynska *
  • Medical University of Lodz, Łódź, Poland

The final, formatted version of the article will be published soon.

    INTRODUCTION: Inflammasomes NLRP1 (NLR family pyrin domain containing 1) and NLRP3 are pivotal regulators of the innate immune response, activated by a spectrum of endogenous and exogenous stressors, including ultraviolet radiation (UVR). The precise molecular mechanisms underlying the activation of these inflammasomes remain unclear. Furthermore, the involvement of interleukin-33 (IL-33) in UVR-induced skin carcinogenesis is not well defined. PURPOSE: The objective of this study is to evaluate the expression of interleukin genes (IL-33, IL-18, IL-1β) following the activation and silencing of NLRP1 and NLRP3 at various wavelengths and doses of UV radiation, and to correlate these expressions with pertinent tumor markers (e.g., Gli1, Gli2, FOXO3A, SerpinA1, SerpinA3, and EphB2).METHODS AND MATERIALS: Cultures of keratinocyte cell lines were exposed to varying doses of UV radiation using specific lamps. To inhibit the expression of NLRP1 and NLRP3 genes, cells were transfected with targeted siRNAs. Gene expression of inflammasome components and effector proteins was quantified using Real-time PCR and ELISA.RESULTS: There was a marked upregulation in the expression levels of cytokine genes IL-18, IL-1β, and IL-33 upon exposure to UVB and UVA radiation, compared to non-irradiated keratinocytes. Silencing NLRP1 or NLRP3 via RNA interference in primary human keratinocytes resulted in a significant reduction of cytokine gene expression. Additionally, a notable increase in tumor marker gene expression was observed in cells with functional NLRP1 and NLRP3 following UV radiation, whereas silencing these inflammasome genes altered the expression profiles of these markers.CONCLUSIONS: This study provides a pioneering comprehensive assessment of the roles of NLRP1, NLRP3, and IL-33 in the pathogenesis of UV-induced cutaneous carcinogenesis. Our findings

    Keywords: Inflammasome, NLRP1, NLRP3, IL-33, Cutaneous carcinogenesis

    Received: 19 Aug 2024; Accepted: 17 Dec 2024.

    Copyright: © 2024 Lesiak, Wodz, Ceryn, Sobolewska -Sztychny, Bednarski, Piekarski, Pabianek, Nejc, Dróżdż, Narbutt, Noweta and Ciazynska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Magdalena Ciazynska, Medical University of Lodz, Łódź, Poland

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