Autor: |
Macarena Orejudo, Raul R. Rodrigues-Diez, Raquel Rodrigues-Diez, Ana Garcia-Redondo, Laura Santos-Sánchez, Javier Rández-Garbayo, Pablo Cannata-Ortiz, Adrian M. Ramos, Alberto Ortiz, Rafael Selgas, Sergio Mezzano, Carolina Lavoz, Marta Ruiz-Ortega |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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Zdroj: |
Frontiers in Pharmacology, Vol 10 (2019) |
Druh dokumentu: |
article |
ISSN: |
1663-9812 |
DOI: |
10.3389/fphar.2019.01015 |
Popis: |
Hypertension is now considered as an inflammatory disease, and the kidney is a key end-organ target. Experimental and clinical studies suggest that interleukin 17A (IL-17A) is a promising therapeutic target in immune and chronic inflammatory diseases, including hypertension and kidney disease. Elevated circulating IL-17A levels have been observed in hypertensive patients. Our aim was to investigate whether chronically elevated circulating IL-17A levels could contribute to kidney damage, using a murine model of systemic IL-17A administration. Blood pressure increased after 14 days of IL-17A infusion in mice when compared with that in control mice, and this was associated to kidney infiltration by inflammatory cells, including CD3+ and CD4+ lymphocytes and neutrophils. Moreover, proinflammatory factors and inflammatory-related intracellular mechanisms were upregulated in kidneys from IL-17A-infused mice. In line with these findings, in the model of angiotensin II infusion in mice, IL-17A blockade, using an anti-IL17A neutralizing antibody, reduced kidney inflammatory cell infiltrates and chemokine overexpression. In kidney biopsies from patients with hypertensive nephrosclerosis, IL-17A positive cells, mainly Th17 and γδ T lymphocytes, were found. Overall, the results support a pathogenic role of IL-17A in hypertensive kidney disease-associated inflammation. Therapeutic approaches targeting this cytokine should be explored to prevent hypertension-induced kidney injury. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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