ANG II receptor blockade enhances anti-inflammatory macrophages in anti-glomerular basement membrane glomerulonephritis
| Autor: | Akiko Mii, T. Arai, Yasuhiro Natori, Akira Shimizu, Yuh Fukuda, Kaoru Aki, Emiko Fujita, Arimi Ishikawa, Yoshitaka Fukunaga, Naomi Kuwahara, Yukinari Masuda |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Angiotensin receptor Physiology Anti-Glomerular Basement Membrane Disease Cell Kidney Glomerulus Tetrazoles Blood Pressure CD8-Positive T-Lymphocytes urologic and male genital diseases Rats Inbred WKY Angiotensin Receptor Antagonists Immune system Renin–angiotensin system medicine Macrophage Animals Inflammation Dose-Response Relationship Drug Chemistry Glomerular basement membrane Macrophages Imidazoles Glomerulonephritis medicine.disease Angiotensin II Rats Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Immunology Cancer research Cytokines Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | American journal of physiology. Renal physiology. 298(4) |
| ISSN: | 1522-1466 |
| Popis: | Macrophages are heterogeneous immune cell populations that include classically activated and alternatively activated (M2) macrophages. We examined the anti-inflammatory effect of ANG II type 1 receptor (AT1R) blocker (ARB) on glomerular inflammation in a rat model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). The study focused on infiltrating CD8+and CD4+cells and macrophages, as well as the heterogeneity of intraglomerular macrophages. Wistar-Kyoto rats were treated with high-dose olmesartan (3 mg·kg−1·day−1), low-dose olmesartan (0.3 mg·kg−1·day−1), or vehicle (control) 7 days before induction of anti-GBM GN. Control rats showed mainly CD8+cells and ED1+macrophages, with a few CD4+cells infiltrating the glomeruli. Necrotizing and crescentic glomerular lesions developed by day 7 with the increase of proteinuria. AT1R was expressed on CD8+and CD4+cells and on ED1+macrophages. Low-dose ARB had no anti-inflammatory effects in anti-GBM GN. However, high-dose ARB reduced glomerular infiltration of CD8+cells and ED1+macrophages and suppressed necrotizing and crescentic lesions by days 5 to 7 ( P < 0.05). In addition, high-dose ARB reduced the numbers of ED3+-activated macrophages, suppressed glomerular TNF-α and IFN-γ production, and downregulated M1-related chemokine and cytokines (monocyte chemoattractant protein type 1, IL-6, and IL-12). High-dose ARB also enhanced ED2+M2 macrophages by day 7 with upregulation of glomerular IL-4 and IL-13 and augmented CCL17, IL-1 receptor antagonist, and IL-10. We concluded that high-dose ARB inhibits glomerular inflammation by increasing the numbers of M2 macrophages and upregulation of anti-inflammatory cytokines and by suppressing M1 macrophage development with downregulation of M1-related proinflammatory cytokines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|