Regulatory role of annexin A1 in NLRP3 inflammasome activation in atopic dermatitis: insights from keratinocytes in human and murine studies

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorFaculdade de Medicina de São José Do Rio Preto (FAMERP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUnião das Faculdades Dos Grandes Lagos (Unilago)-
Autor(es): dc.contributorUniversity College London (UCL)-
Autor(es): dc.creatorCorreia-Silva, Rebeca D.-
Autor(es): dc.creatorCorrêa, Mab P.-
Autor(es): dc.creatorde Castro, Maria Eduarda-
Autor(es): dc.creatorAlmeida, Joaquim S.-
Autor(es): dc.creatorD’Ávila, Solange C. G. P.-
Autor(es): dc.creatorOliani, Sonia M.-
Autor(es): dc.creatorGreco, Karin V.-
Autor(es): dc.creatorGil, Cristiane D.-
Data de aceite: dc.date.accessioned2025-08-21T23:32:07Z-
Data de disponibilização: dc.date.available2025-08-21T23:32:07Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1007/s00109-025-02529-w-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/304876-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/304876-
Descrição: dc.descriptionAbstract: Despite the well-documented regulatory role of annexin A1 (ANXA1) in numerous stages of the inflammatory response, its involvement in regulating the NLRP3 inflammasome in the context of allergic responses has not been extensively investigated to date. This study evaluated the expression patterns of the ANXA1 and NLRP3 proteins in human skin samples obtained from patients with atopic dermatitis (AD) and in mice with ovalbumin (OVA)-induced experimental AD. Furthermore, the in vitro effect of the ANXA1 mimetic peptide Ac2-26 on IL-4-stimulated human keratinocytes was evaluated. IL-4-stimulated keratinocytes were treated with Ac2-26 (a mimetic peptide of ANXA1) in two different concentrations: 5 and 25 ng/mL. Additionally, some cells were treated with the pan-formyl peptide receptor antagonist Boc2 at a concentration of 10 µM, administered 15 min before Ac2-26. The NLRP3 protein demonstrated intense immunoreactivity in both murine and human AD skin samples, with NLRP3 and ANXA1 exhibiting particularly high coexpression in keratinocytes. A significant increase in ANXA1 and NLRP3 transcripts was observed in AD skins (GSE16161 study). ANXA1 transcript levels were elevated in the AD epidermis relative to the non-lesional epidermis, while NLRP3 transcript levels were reduced in the AD epidermis (GSE120721 study). The Ac2-26 treatment reduced the proliferation rate of IL-4-stimulated keratinocytes, an effect abolished by Boc2 and IL-1β and ROS production. In conclusion, our findings indicate that ANXA1 plays a role in regulating NLRP3 activation in keratinocytes, contributing to the pathogenesis of AD. Key messages: ANXA1 and NLRP3 levels are upregulated and exhibit coexpression in murine and human AD skins. ANXA1-FPR axis regulates the proliferation of human keratinocytes under IL-4 stimulation. ANXA1-derived peptide Ac2-26 regulates oxidative stress and NLRP3 activation in human keratinocytes.-
Descrição: dc.descriptionDepartamento de Morfologia E Genética Escola Paulista de Medicina (EPM) Universidade Federal de São Paulo (UNIFESP), Rua Botucatu 740, Ed. Lemos Torres – 3º andar, SP-
Descrição: dc.descriptionDepartamento de Patologia EPM-UNIFESP, SP-
Descrição: dc.descriptionDepartamento de Patologia E Medicina Forense Faculdade de Medicina de São José Do Rio Preto (FAMERP), SP-
Descrição: dc.descriptionInstituto de Biociências Universidade Estadual Paulista (UNESP), Letras E Ciências Exatas, SP-
Descrição: dc.descriptionCentro de Pesquisa Avançada Em Medicina (CEPAM) União das Faculdades Dos Grandes Lagos (Unilago), São Paulo-
Descrição: dc.descriptionDivision of Surgery and Interventional Science University College London (UCL)-
Descrição: dc.descriptionInstituto de Biociências Universidade Estadual Paulista (UNESP), Letras E Ciências Exatas, SP-
Idioma: dc.languageen-
Relação: dc.relationJournal of Molecular Medicine-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectANXA1-
Palavras-chave: dc.subjectFPR-
Palavras-chave: dc.subjectIL-4-
Palavras-chave: dc.subjectKeratinocyte-
Palavras-chave: dc.subjectNLRP3-
Palavras-chave: dc.subjectSkin-
Palavras-chave: dc.subjectTranscriptome-
Título: dc.titleRegulatory role of annexin A1 in NLRP3 inflammasome activation in atopic dermatitis: insights from keratinocytes in human and murine studies-
Tipo de arquivo: dc.typelivro digital-
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