| Texto completo | |
| Autor(es): |
Ramos, Yasmim Alefe Leuzzi
;
Pereira, Naiura Vieira
;
Aoki, Valeria
;
Sotto, Mirian Nacagami
;
Kawakami, Joyce Tiyeko
;
da Silva, Luiz Fernando Ferraz
;
Sato, Maria Notomi
;
Orfali, Raquel Leao
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ARCHIVES OF DERMATOLOGICAL RESEARCH; v. 316, n. 5, p. 5-pg., 2024-05-11. |
| Resumo | |
Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1 beta and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1 beta, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1 beta expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1 beta (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1 beta, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1 beta, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1 beta in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions. (AU) | |
| Processo FAPESP: | 18/23211-0 - Avaliação do perfil dos inflamassomas nas lesões cutâneas de dermatite atópica no adulto |
| Beneficiário: | Valeria Aoki |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |