New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis
IntroductionInflammasomes 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 t...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1483208/full |
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| author | Aleksandra Lesiak Aleksandra Lesiak Karolina Wodz Justyna Ceryn Dorota Sobolewska-Sztychny Dorota Sobolewska-Sztychny Igor Bednarski Janusz Piekarski Marta Pabianek Dariusz Nejc Izabela Dróżdż Joanna Narbutt Marcin Noweta Magdalena Ciążyńska Magdalena Ciążyńska |
| author_facet | Aleksandra Lesiak Aleksandra Lesiak Karolina Wodz Justyna Ceryn Dorota Sobolewska-Sztychny Dorota Sobolewska-Sztychny Igor Bednarski Janusz Piekarski Marta Pabianek Dariusz Nejc Izabela Dróżdż Joanna Narbutt Marcin Noweta Magdalena Ciążyńska Magdalena Ciążyńska |
| author_sort | Aleksandra Lesiak |
| collection | DOAJ |
| description | IntroductionInflammasomes 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.PurposeThe 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 materialsCultures 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.ResultsThere 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.ConclusionThis 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 substantiate the role of IL-33 as a critical early danger signal elicited in response to inflammatory UV radiation, presumably regulated by inflammasomes. |
| format | Article |
| id | doaj-art-f8c16b3075e44bc689b27a4c0d4798fb |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-f8c16b3075e44bc689b27a4c0d4798fb2025-01-07T06:45:44ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011110.3389/fmed.2024.14832081483208New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesisAleksandra Lesiak0Aleksandra Lesiak1Karolina Wodz2Justyna Ceryn3Dorota Sobolewska-Sztychny4Dorota Sobolewska-Sztychny5Igor Bednarski6Janusz Piekarski7Marta Pabianek8Dariusz Nejc9Izabela Dróżdż10Joanna Narbutt11Marcin Noweta12Magdalena Ciążyńska13Magdalena Ciążyńska14Department of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandLaboratory of Autoinflammatory, Genetic and Rare Skin Disorders Medical University of Łódź, Łódź, PolandLaboratory of Molecular Biology, Vet-Lab Brudzew, Brudzew, PolandDepartment of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandDepartment of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandLaboratory of Autoinflammatory, Genetic and Rare Skin Disorders Medical University of Łódź, Łódź, PolandDepartment of Neurology, Medical University of Lodz, Łódź, PolandDepartment of Surgical Oncology, Central Teaching Hospital of the Medical University of Lodz, Łódź, PolandChemotherapy Sub-Department and One-Day Chemotherapy Department, Specialist Oncological Hospital NU-MED sp. z o. o., Tomaszów Mazowiecki, PolandDepartment of Surgical Oncology, Central Teaching Hospital of the Medical University of Lodz, Łódź, PolandDepartment of Clinical Genetics, Medical University of Lodz, Łódź, PolandDepartment of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandDepartment of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandDepartment of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, PolandChemotherapy Sub-Department and One-Day Chemotherapy Department, Specialist Oncological Hospital NU-MED sp. z o. o., Tomaszów Mazowiecki, PolandIntroductionInflammasomes 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.PurposeThe 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 materialsCultures 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.ResultsThere 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.ConclusionThis 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 substantiate the role of IL-33 as a critical early danger signal elicited in response to inflammatory UV radiation, presumably regulated by inflammasomes.https://www.frontiersin.org/articles/10.3389/fmed.2024.1483208/fullinflammasomeNLRP1NLRP3IL-33cutaneous carcinogenesis |
| spellingShingle | Aleksandra Lesiak Aleksandra Lesiak Karolina Wodz Justyna Ceryn Dorota Sobolewska-Sztychny Dorota Sobolewska-Sztychny Igor Bednarski Janusz Piekarski Marta Pabianek Dariusz Nejc Izabela Dróżdż Joanna Narbutt Marcin Noweta Magdalena Ciążyńska Magdalena Ciążyńska New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis Frontiers in Medicine inflammasome NLRP1 NLRP3 IL-33 cutaneous carcinogenesis |
| title | New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis |
| title_full | New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis |
| title_fullStr | New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis |
| title_full_unstemmed | New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis |
| title_short | New insight into the role of the pathway NLRP1 and NLRP3 inflammasomes and IL-33 in ultraviolet-induced cutaneous carcinogenesis |
| title_sort | new insight into the role of the pathway nlrp1 and nlrp3 inflammasomes and il 33 in ultraviolet induced cutaneous carcinogenesis |
| topic | inflammasome NLRP1 NLRP3 IL-33 cutaneous carcinogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1483208/full |
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