Autor(es)

Correia-Silva, Rebeca D. ; Correa, Mab P. ; Rodrigues-Silva, Nathalia ; Santos, Diego D. ; D'Avila, Solange C. G. P. ; Greco, Karin V. ; Gil, Cristiane D.

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 159, p. 12-pg., 2025-06-26.

Resumo

Psoriasis (Pso) is a chronic inflammatory skin disease involving immune dysregulation and epidermal hyperplasia. Annexin A1 (ANXA1), a glucocorticoid-regulated protein, and S100A11 are implicated in keratinocyte function, but their roles in Pso remain unclear. This study translationally elucidates the functional role of ANXA1 and S100A11 in Pso by integrating analyses in human and murine skin biopsies and in vitro assays using human keratinocytes. The expression patterns of the ANXA1 and S100A11 in Pso were investigated using an imiquimod (IMQ)- induced murine model and human skin biopsies. Furthermore, the in vitro effect of the ANXA1-derived peptide Ac2-26 (5, 25, and 50 ng/mL) on IL-17-stimulated human keratinocytes (HaCaT cell line) was evaluated. IMQ-treated mice exhibited hallmark psoriatic features, including epidermal thickening, mast cell degranulation, and elevated IL-23 levels. Immunohistochemical analyses revealed significant upregulation of ANXA1 and S100A11 in psoriatic skin, with coexpression observed in keratinocytes, particularly in superficial epidermal layers. Transcriptomic analysis corroborated these findings, showing elevated ANXA1 and S100A11 expression in psoriatic lesions compared to controls. In HaCaT cells, IL-17 stimulation reduced ANXA1 and S100A11 levels. Treatment with Ac2-26 at the highest concentrations (25 and 50 ng/mL) significantly reduced viability/metabolism of IL-17-stimulated keratinocytes, while the lowest concentration of Ac2-26 (5 ng/mL) effectively increased ROS production. In conclusion, ANXA1 and S100A11 are key players in Pso, with their expression and coexpression closely linked to disease pathogenesis. Further studies are warranted to explore the clinical implications of targeting the ANXA1/S100A11 axis in inflammatory skin diseases. (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