Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy.

Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy. Int Immunopharmacol. 2015 Jan 15; Authors: Cucak H, Nielsen Fink L, Højgaard Pedersen M, Rosendahl A Abstract Diabetic nephropathy (DN) is a serious complication of longstanding diabetes affecting up to 30% of all diabetes patients and is the main cause of end-stage kidney disease globally. Current standard treatment e.g. ACE-inhibitors like enalapril merely offers a delay in the progression leading to DN. Herein, we describe in two preclinical models evidence to local effects on the inflammatory signatures after intervention treatment with enalapril which provides enhanced understanding of the mechanism of ACE inhibitors. Enalapril transiently reduced albuminuria in both the db/db and the STZ-induced DN models with established disease, without modulating the HbA1c%. Albuminuria was strongly associated with loss of leukocytes, particularly B cells, but also of sub-populations of macrophages and CD4(+) T cells. The remaining kidney macrophages were polarized into a M2-like sub-population with reduced surface expression of the M1-like macrophage marker CD11c and enhanced expression of galectin-3. Enalapril treatment counteracted the reduction of leukocytes in the diabetic kidney towards levels noted in the non-diabetic kidney. Particularly, a subset of macrophages was increased and a clear expansion of CD4...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research