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Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy.
- Source :
- Diabetes; Feb2017, Vol. 66 Issue 2, p494-504, 11p, 8 Graphs
- Publication Year :
- 2017
-
Abstract
- Diabetic nephropathy (DN) is characterized by increased macrophage infiltration, and proinflammatory M1 macrophages contribute to development of DN. Previous studies by us and others have reported that macrophage cyclooxygenase-2 (COX-2) plays a role in polarization and maintenance of a macrophage tissue-reparative M2 phenotype. We examined the effects of macrophage COX-2 on development of DN in type 1 diabetes. Cultured macrophages with COX-2 deletion exhibited an M1 phenotype, as demonstrated by higher inducible nitric oxide synthase and nuclear factor-κB levels but lower interleukin-4 receptor-α levels. Compared with corresponding wild-type diabetic mice, mice with COX-2 deletion in hematopoietic cells (COX-2 knockout bone marrow transplantation) or macrophages (CD11b-Cre COX2f/f) developed severe DN, as indicated by increased albuminuria, fibrosis, and renal infiltration of T cells, neutrophils, and macrophages. Although diabetic kidneys with macrophage COX-2 deletion had more macrophage infiltration, they had fewer renal M2 macrophages. Diabetic kidneys with macrophage COX-2 deletion also had increased endoplasmic reticulum stress and decreased number of podocytes. Similar results were found in diabetic mice with macrophage PGE2 receptor subtype 4 deletion. In summary, these studies have demonstrated an important but unexpected role for macrophage COX-2/prostaglandin E2/PGE2 receptor subtype 4 signaling to lessen progression of diabetic kidney disease, unlike the pathogenic effects of increased COX-2 expression in intrinsic renal cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- MACROPHAGES
CYCLOOXYGENASE 2
DIABETIC nephropathies
PROSTAGLANDINS
NEUTROPHILS
PROTEIN expression
PREVENTION
ALBUMINURIA
ANIMAL experimentation
ANIMALS
CELL culture
CELL receptors
CELLULAR signal transduction
DIABETES
IMMUNITY
IMMUNOBLOTTING
IMMUNOHISTOCHEMISTRY
TYPE 1 diabetes
KIDNEYS
MICE
OXIDOREDUCTASES
POLYMERASE chain reaction
RESEARCH funding
T cells
DNA-binding proteins
FIBROSIS
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 66
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 120841475
- Full Text :
- https://doi.org/10.2337/db16-0773