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Article: Rapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 mice

TitleRapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 mice
Authors
KeywordsAutoimmunity
Lupus nephritis
NZB/W F1 mice
Rapamycin
Issue Date2008
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2008, v. 23 n. 9, p. 2768-2776 How to Cite?
AbstractBackground. Rapamycin is a potent immunosuppressive drug with proven efficacy in rejection prophylaxis in solid organ transplantation. By virtue of its immunosuppressive properties, rapamycin might also be useful in the treatment of autoimmune diseases. The aim of this study was to determine the effect of rapamycin on the severity of established nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Methods. Six-month-old female NZB/W F1 mice with active nephritis (albuminuria >100 mg/dL) were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 4 months. The effect of rapamycin on the severity of nephritis was evaluated by clinical manifestations, biochemical parameters, renal histology, immunohistochemistry and semi-quantitative gene expression studies. Results. Treatment with rapamycin significantly decreased albuminuria, improved survival, diminished splenomegaly, preserved renal function and reduced serum anti-dsDNA antibody levels. Kidney sections from saline-treated mice revealed marked mesangial proliferation, tubular dilation with intra-tubular protein cast deposition and leukocytic infiltration of the interstitium. The rapamycin-treated mice, in contrast, had relatively mild histological changes in their kidneys. Rapamycin treatment also significantly reduced the amount of immune complex deposition in the glomeruli, suppressed the interstitial infiltration by T-cells, B-cells and macrophages as well as down-regulated the intra-renal expression of RANTES. Conclusions. We conclude that rapamycin is effective in attenuating the severity of established nephritis in NZB/W F 1 mice. The beneficial effects of rapamycin are mediated, at least in part, through inhibition of lymphoproliferation, reduced RANTES expression and decreased inflammatory cell infiltration in the kidneys. Rapamycin could be of therapeutic value in the treatment of human lupus nephritis. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/77945
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
Funding AgencyGrant Number
RGC Competitive Earmarked Research GrantHKU 7550/06M
Hong Kong Society of Nephrology
Wai Hung Charity Foundation
Funding Information:

This study was supported by research grants from the RGC Competitive Earmarked Research Grant (HKU 7550/06M), the Hong Kong Society of Nephrology and the Wai Hung Charity Foundation.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLui, SLen_HK
dc.contributor.authorTsang, Ren_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorZhang, Fen_HK
dc.contributor.authorTam, Sen_HK
dc.contributor.authorYung, Sen_HK
dc.contributor.authorChan, TMen_HK
dc.date.accessioned2010-09-06T07:37:28Z-
dc.date.available2010-09-06T07:37:28Z-
dc.date.issued2008en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2008, v. 23 n. 9, p. 2768-2776en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77945-
dc.description.abstractBackground. Rapamycin is a potent immunosuppressive drug with proven efficacy in rejection prophylaxis in solid organ transplantation. By virtue of its immunosuppressive properties, rapamycin might also be useful in the treatment of autoimmune diseases. The aim of this study was to determine the effect of rapamycin on the severity of established nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Methods. Six-month-old female NZB/W F1 mice with active nephritis (albuminuria >100 mg/dL) were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 4 months. The effect of rapamycin on the severity of nephritis was evaluated by clinical manifestations, biochemical parameters, renal histology, immunohistochemistry and semi-quantitative gene expression studies. Results. Treatment with rapamycin significantly decreased albuminuria, improved survival, diminished splenomegaly, preserved renal function and reduced serum anti-dsDNA antibody levels. Kidney sections from saline-treated mice revealed marked mesangial proliferation, tubular dilation with intra-tubular protein cast deposition and leukocytic infiltration of the interstitium. The rapamycin-treated mice, in contrast, had relatively mild histological changes in their kidneys. Rapamycin treatment also significantly reduced the amount of immune complex deposition in the glomeruli, suppressed the interstitial infiltration by T-cells, B-cells and macrophages as well as down-regulated the intra-renal expression of RANTES. Conclusions. We conclude that rapamycin is effective in attenuating the severity of established nephritis in NZB/W F 1 mice. The beneficial effects of rapamycin are mediated, at least in part, through inhibition of lymphoproliferation, reduced RANTES expression and decreased inflammatory cell infiltration in the kidneys. Rapamycin could be of therapeutic value in the treatment of human lupus nephritis. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.rightsNephrology, Dialysis, Transplantation. Copyright © Oxford University Press.en_HK
dc.subjectAutoimmunityen_HK
dc.subjectLupus nephritisen_HK
dc.subjectNZB/W F1 miceen_HK
dc.subjectRapamycinen_HK
dc.subject.meshAlbuminuria - drug therapyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAutoimmunityen_HK
dc.subject.meshChemokine CCL5 - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshImmunosuppressive Agents - pharmacology - therapeutic useen_HK
dc.subject.meshKidney - metabolismen_HK
dc.subject.meshLupus Nephritis - drug therapy - pathologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred NZBen_HK
dc.subject.meshNephritisen_HK
dc.subject.meshSirolimus - pharmacology - therapeutic useen_HK
dc.subject.meshSplenomegalyen_HK
dc.titleRapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0931-0509&volume=23&spage=2768&epage=2776&date=2008&atitle=Rapamycin+attenuates+the+severity+of+established+nephritis+in+lupus-prone+NZB/W+F1+miceen_HK
dc.identifier.emailChan, KW:hrmtckw@hku.hken_HK
dc.identifier.emailYung, S:ssyyung@hku.hken_HK
dc.identifier.emailChan, TM:dtmchan@hku.hken_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfn216en_HK
dc.identifier.pmid18445640-
dc.identifier.scopuseid_2-s2.0-58549107810en_HK
dc.identifier.hkuros150365en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58549107810&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2768en_HK
dc.identifier.epage2776en_HK
dc.identifier.eissn1460-2385-
dc.identifier.isiWOS:000259372400014-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectEffect of rapamycin, alone or in combination with mycophenolate mofetil, in the treatment of murine lupus nephritis-
dc.identifier.scopusauthoridLui, SL=7102379130en_HK
dc.identifier.scopusauthoridTsang, R=7102940073en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridZhang, F=25522980800en_HK
dc.identifier.scopusauthoridTam, S=7202037323en_HK
dc.identifier.scopusauthoridYung, S=22636568800en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK

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