Abstract:
:Expression of the inducible form of nitric oxide synthase (iNOS) has been found to be up-regulated in cytokine-stimulated mesangial cells (MC) and in experimental glomerulonephritis. Since direct toxicity of nitric oxide (NO) has been implicated in damage of bacteria, neoplastic and intact pancreatic cells, we investigated whether NO is cytotoxic to cultured MC, which may be relevant to pathogenesis of glomerular injury. MC isolated from rat glomeruli generated substantial amounts of nitrite, the stable NO end-product, when cells were stimulated with IL-1beta and tumour necrosis factor-alpha (TNF-alpha). Total DNA synthesis was significantly reduced in the presence of IL-1beta and TNF-alpha, and this effect was completely reversed by N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of iNOS. Stimulation of MC with IL-1beta and TNF-alpha caused remarkable toxicity to these cells, measured by the MTT test (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide cleavage, specific cytotoxicity 41.5 +/- 20.3%), and much less prominent MC lysis (3H-thymidine release, specific cytolysis 11.5 +/- 5.3%). Toxic effects of cytokines were fully reversible by the iNOS inhibitor. Lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), but not IL-1beta and TNF-alpha, induced rat peritoneal macrophages to produce large amounts of nitrite. In co-culture, such prestimulated macrophages had significantly cytotoxic (MTT test 62.9 +/- 19.9%) and cytolytic (3H-thymidine release 57.9 +/- 13.8%) effects on MC. Again, this toxicity was totally inhibited in the presence of L-NMMA. We conclude from these results that cytokine-stimulated generation of NO by MC or macrophages is directly toxic to MC, and may play a role in pathogenesis of glomerular injury involving mesangiolysis.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Hruby Z,Beck KFdoi
10.1046/j.1365-2249.1997.d01-906.xsubject
Has Abstractpub_date
1997-01-01 00:00:00pages
76-82issue
1eissn
0009-9104issn
1365-2249journal_volume
107pub_type
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
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doi:10.1111/j.1365-2249.1994.tb06134.x
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1995.tb05573.x
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
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更新日期:2015-11-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1992.tb06969.x
更新日期:1992-09-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:2007-02-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1365-2249.2004.02602.x
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1995.tb03860.x
更新日期:1995-12-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00
abstract::A method is described for culturing intact human thyroid follicles, based on the study of 40 thyroidectomy specimens from normal (n = 18) and diseased glands (n = 22). Reversal of the normal polarity of thyrocytes, whereby the microvilli move from the colloid edge to the vascular pole of the cells, occurs gradually wh...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
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pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1996.909604.x
更新日期:1996-01-01 00:00:00