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

Autor: Elena González‐Sánchez, Antonio Muñoz‐Callejas, Javier Gómez‐Román, Esther San Antonio, Alessandro Marengo, Nicolas Tsapis, Kamila Bohne‐Japiassu, Rafael González‐Tajuelo, Saray Pereda, Javier García‐Pérez, Lorenzo Cavagna, Miguel Ángel González‐Gay, Esther Francisca Vicente‐Rabaneda, Federica Meloni, Elias Fattal, Santos Castañeda, Ana Urzainqui
Rok vydání: 2022
Předmět:
Zdroj: British Journal of Pharmacology. 179:4534-4548
ISSN: 1476-5381
0007-1188
DOI: 10.1111/bph.15898
Popis: 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.Aged PSGL-1 KO (SelplgPSGL-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.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.
Databáze: OpenAIRE
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