Statin attenuates experimental anti-glomerular basement membrane glomerulonephritis together with the augmentation of alternatively activated macrophages
| Autor: | Kaoru Aki, Emiko Fujita, Akira Shimizu, Shinya Nagasaka, Yasuhiko Iino, Yasuo Katayama, T. Arai, Akiko Mii, Yasuhiro Natori, Yuh Fukuda, Naomi Kuwahara, Yukinari Masuda |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Anti-Glomerular Basement Membrane Disease medicine.medical_treatment Rats Inbred WKY Statistics Nonparametric Pathology and Forensic Medicine Internal medicine Glomerular Basement Membrane Correspondence medicine Atorvastatin Animals Pyrroles RNA Messenger Basement membrane biology Reverse Transcriptase Polymerase Chain Reaction Monocyte Glomerular basement membrane Macrophages Glomerulonephritis medicine.disease Immunohistochemistry Rats Microscopy Electron Cytokine medicine.anatomical_structure Endocrinology Heptanoic Acids biology.protein Cytokines Tumor necrosis factor alpha Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | The American journal of pathology. 177(3) |
| ISSN: | 1525-2191 |
| Popis: | Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1 also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. In contrast, statin reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages. |
| Databáze: | OpenAIRE |
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