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 Detalle_Publicacion

Targeted nanotherapy with everolimus reduces inflammation and fibrosis in scleroderma-related interstitial lung disease developed by PSGL-1 deficient mice

Abstract: Background and purpose: Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc-like syndrome with high incidence of ILD in aged mice. Experimental approach: Aged PSGL-1 KO (Selplg-/- ) mice were used to assess the therapeutic effects of nanotherapy with everolimus, included in liposomes decorated with high MW hyaluronic acid (LipHA+Ev) and administered intratracheally to specifically target CD44-expressing lung cells. Key results: PSGL-1 KO mice had increased numbers of CD45+ and CD45- cells, including alveolar and interstitial macrophages, eosinophils, granulocytes and NK cells, and myofibroblasts in bronchoalveolar lavage (BAL). CD45+ and CD45- cells expressing pro-inflammatory and pro-fibrotic cytokines were also increased. Lungs from PSGL-1 KO mice showed increased immune cell infiltration and apoptosis and exacerbated interstitial and peribronchial fibrosis. Targeted nanotherapy with LipHA+Ev decreased the myofibroblasts in BAL, cells producing proinflammatory and profibrotic cytokines, and the degree of lung inflammation at histology. LipHA+Ev treatment also decreased the severity of peribronchial and interstitial lung fibrosis, from moderate to mild levels. Conclusions and implications: In PSGL-1 KO mice, targeted nanotherapy with LipHA+Ev was an effective treatment for SSc-ILD, reducing the number of inflammatory and fibrotic cells in BAL and reducing inflammation and fibrosis in lungs.

 Fuente: British Journal of Pharmacology, 2022, 179(18), 4534-4548

Editorial: Wiley

 Año de publicación: 2022

Nº de páginas: 15

Tipo de publicación: Artículo de Revista

 DOI: 10.1111/bph.15898

ISSN: 0007-1188,1476-5381

Url de la publicación: https://doi.org/10.1111/bph.15898

Autores/as

GONZÁLEZ-SÁNCHEZ, ELENA

MUÑOZ-CALLEJAS, ANTONIO

SAN ANTONIO, ESTHER

MARENGO, ALESSANDRO

TSAPIS, NICOLAS

BOHNE-JAPIASSU, KAMILA

GONZÁLEZ-TEJUELO, RAFAEL

SARAY PEREDA MARCOS

GARCÍA-PÉREZ, JAVIER

VICENTE-RABANEDA, ESTHER FRANCISCA

MELONI, FEDERICA

FATTAL, ELÍAS

CASTAÑEDA, SANTOS

URZAINQUI, ANA