Interleukin 17A Participates in Renal Inflammation Associated to Experimental and Human Hypertension

Orejudo M.; Rodrigues-Diez R.R.; Rodrigues-Diez R.; Garcia-Redondo A.; Santos-Sánchez L.; Rández-Garbayo J.; Cannata-Ortiz P.; Ramos A.M.; Ortiz A.; Selgas R.; Mezzano S.; Lavoz C.; Ruiz-Ortega M.

Abstract

Hypertension is now considered as an inflammatory disease, and the kidney is a key endorgan 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 gamma delta 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.

Más información

Título según WOS: Interleukin 17A Participates in Renal Inflammation Associated to Experimental and Human Hypertension
Título según SCOPUS: Interleukin 17A participates in renal inflammation associated to experimental and human hypertension
Título de la Revista: FRONTIERS IN PHARMACOLOGY
Volumen: 10
Editorial: FRONTIERS MEDIA SA
Fecha de publicación: 2019
Idioma: English
DOI:

10.3389/fphar.2019.01015

Notas: ISI, SCOPUS