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Article: IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat

TitleIL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat
Authors
Issue Date1999
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal of Pathology, 1999, v. 154 n. 3, p. 833-841 How to Cite?
AbstractOsteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence that IL-1 up-regulates OPN expression in experimental kidney disease and support for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury.
Persistent Identifierhttp://hdl.handle.net/10722/49100
ISSN
2015 Impact Factor: 4.206
2015 SCImago Journal Rankings: 2.653
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYu, XQen_HK
dc.contributor.authorFan, JMen_HK
dc.contributor.authorNikolic-Paterson, DJen_HK
dc.contributor.authorYang, Nen_HK
dc.contributor.authorMu, Wen_HK
dc.contributor.authorPichler, Ren_HK
dc.contributor.authorJohnson, RJen_HK
dc.contributor.authorAtkins, RCen_HK
dc.contributor.authorLan, HYen_HK
dc.date.accessioned2008-06-12T06:34:25Z-
dc.date.available2008-06-12T06:34:25Z-
dc.date.issued1999en_HK
dc.identifier.citationAmerican Journal of Pathology, 1999, v. 154 n. 3, p. 833-841en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49100-
dc.description.abstractOsteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence that IL-1 up-regulates OPN expression in experimental kidney disease and support for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAnti-Glomerular Basement Membrane Disease - metabolism - pathologyen_HK
dc.subject.meshInterleukin-1 - physiologyen_HK
dc.subject.meshSialoglycoproteins - antagonists & inhibitors - metabolism - pharmacologyen_HK
dc.subject.meshDisease Progressionen_HK
dc.subject.meshEpithelial Cells - drug effects - metabolismen_HK
dc.titleIL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the raten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9440&volume=154&issue=3&spage=833&epage=841&date=1999&atitle=IL-1+up-regulates+osteopontin+expression+in+experimental+crescentic+glomerulonephritis+in+the+raten_HK
dc.identifier.emailLan, HY: hylan@hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid10079261-
dc.identifier.pmcidPMC1866418en_HK
dc.identifier.scopuseid_2-s2.0-0033034335-
dc.identifier.hkuros47115-
dc.identifier.isiWOS:000079021300021-

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