| Statin attenuates experimental anti-glomerular basement membrane glomerulonephritis together with the augmentation of alternatively activated macrophages. | |
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MedLine Citation:
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PMID: 20696778 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Emiko Fujita; Akira Shimizu; Yukinari Masuda; Naomi Kuwahara; Takashi Arai; Shinya Nagasaka; Kaoru Aki; Akiko Mii; Yasuhiro Natori; Yasuhiko Iino; Yasuo Katayama; Yuh Fukuda |
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Publication Detail:
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Type: Journal Article Date: 2010-08-09 |
Journal Detail:
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Title: The American journal of pathology Volume: 177 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-12-13 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1143-54 Citation Subset: AIM; IM |
Affiliation:
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Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Glomerular Basement Membrane Disease / drug therapy*, metabolism, pathology Cytokines / genetics, metabolism Glomerular Basement Membrane / drug effects*, metabolism, pathology Heptanoic Acids / pharmacology, therapeutic use* Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology, therapeutic use Immunohistochemistry Macrophages / drug effects*, metabolism, pathology Male Microscopy, Electron Pyrroles / pharmacology, therapeutic use* RNA, Messenger / genetics, metabolism Rats Rats, Inbred WKY Reverse Transcriptase Polymerase Chain Reaction Statistics, Nonparametric |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 0/RNA, Messenger; 110862-48-1/atorvastatin |
| Comments/Corrections | |
Comment In:
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Am J Pathol. 2011 May;178(5):2447; author reply 2447-8
[PMID:
21514453
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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