Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights.
Autor: | Gouda MM; Department of Psychiatry, University Hospital Bonn, University of Bonn, Venusberg Campus 1, Building 76, 53127, Bonn, Germany. mgouda@uni-bonn.de.; Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India. mgouda@uni-bonn.de., Balaya RDA; Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India., Modi PK; Centre of Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to Be University), Deralakatte, Mangalore, 575018, Karnataka, India., Kadri S; Helmholtz Institute of Regenerative Biology and Medicine, Helmholtz-Zentrum München, 81377, München, Germany., Chanderasekaran J; Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University, Porur, Chennai, India., Balnadupete A; Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India., Bhandary YP; Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India. yash28bhandary@gmail.com. |
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Jazyk: | angličtina |
Zdroj: | Inflammation [Inflammation] 2024 Oct 19. Date of Electronic Publication: 2024 Oct 19. |
DOI: | 10.1007/s10753-024-02167-3 |
Abstrakt: | Acute lung injury (ALI) is primarily driven by an intense inflammation in the alveolar epithelium. Key to this is the pro-inflammatory cytokine, Interleukin 17 (IL-17), which influences pulmonary immunity and modifies p53 function. The direct role of IL-17A in p53-fibrinolytic system is still unclear, it is important to evaluate this mechanism to regulate the ALI progression to idiopathic pulmonary fibrosis (IPF). C57BL/6 mice, exposed to recombinant IL-17A protein and treated with curcumin, provided insight into IL-17A mechanisms and curcumin's potential for modulating early pulmonary fibrosis stages. A diverse methodology, including proteomics, single-cell RNA sequencing (scRNA-seq) integration, molecular, and Schroedinger approach were utilized. In silico approaches facilitated the potential interactions between curcumin, IL-17A, and apoptosis-related proteins. A notable surge in the expression levels of IL-17A, p53, and fibrinolytic components such as Plasminogen Activator Inhibitor-1 (PAI-I) was discerned upon the IL17A exposure in mouse lungs. Furthermore, the enrichment of pathways and differential expression of proteins underscored the significance of IL-17A in governing downstream regulatory pathways such as inflammation, NF-kappaB signaling, Mitogen-Activated Protein Kinases (MAPK), p53, oxidative phosphorylation, JAK-STAT, and apoptosis. The integration of scRNA-seq data from 20 IPF and 10 control lung specimens emphasized the importance of IL-17A mediated downstream regulation in PF patients. A potent immuno-pharmacotherapeutic agent, curcumin, demonstrated a substantial capacity to modulate the lung pathology and molecular changes induced by IL-17A in mouse lungs. Human IPF single cell data integration confirmed the effects of IL-17A mediated fibrinolytic components in ALI to IPF progression. (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
Databáze: | MEDLINE |
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