Autor(es)

Correia-Silva, Rebeca D. ; Correa, Mab P. ; de Castro, Maria Eduarda ; Almeida, Joaquim S. ; D'avila, Solange C. G. P. ; Oliani, Sonia M. ; Greco, Karin V. ; Gil, Cristiane D.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 103, n. 4, p. 17-pg., 2025-03-18.

Resumo

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 mu M, 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-1 beta 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. (AU)

• Processo FAPESP: 21/03847-0 - Papel da anexina A1 e do inflamassoma NLRP3 em doenças inflamatórias da pele: estudo em biópsias de pacientes e modelo in vitro
• Beneficiário: Rebeca Donizete Correia da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/26872-5 - Estudo de proteínas anti-inflamatórias e proinflamatórias como possíveis alvos terapêuticos em modelos experimentais de neuroinflamação e inflamação cutânea
• Beneficiário: Cristiane Damas Gil
• Modalidade de apoio: Auxílio à Pesquisa - Regular