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Article: Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: Implications on tubulointerstitial inflammation in lupus nephritis

TitleEffect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: Implications on tubulointerstitial inflammation in lupus nephritis
Authors
Issue Date2005
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2005, v. 16 n. 11, p. 3281-3294 How to Cite?
AbstractThis study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-α, IL-1β, and IL-6 secretion (P < 0.05). Early induction of TNF-α was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-α, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis. Copyright © 2005 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/162947
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYung, Sen_US
dc.contributor.authorTsang, RCWen_US
dc.contributor.authorSun, Yen_US
dc.contributor.authorLeung, JKHen_US
dc.contributor.authorChan, TMen_US
dc.date.accessioned2012-09-05T05:25:44Z-
dc.date.available2012-09-05T05:25:44Z-
dc.date.issued2005en_US
dc.identifier.citationJournal Of The American Society Of Nephrology, 2005, v. 16 n. 11, p. 3281-3294en_US
dc.identifier.issn1046-6673en_US
dc.identifier.urihttp://hdl.handle.net/10722/162947-
dc.description.abstractThis study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-α, IL-1β, and IL-6 secretion (P < 0.05). Early induction of TNF-α was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-α, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis. Copyright © 2005 by the American Society of Nephrology.en_US
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.orgen_US
dc.relation.ispartofJournal of the American Society of Nephrologyen_US
dc.titleEffect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: Implications on tubulointerstitial inflammation in lupus nephritisen_US
dc.typeArticleen_US
dc.identifier.emailYung, S:ssyyung@hku.hken_US
dc.identifier.emailChan, TM:dtmchan@hku.hken_US
dc.identifier.authorityYung, S=rp00455en_US
dc.identifier.authorityChan, TM=rp00394en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1681/ASN.2004110917en_US
dc.identifier.scopuseid_2-s2.0-33644878084en_US
dc.identifier.hkuros112132-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33644878084&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume16en_US
dc.identifier.issue11en_US
dc.identifier.spage3281en_US
dc.identifier.epage3294en_US
dc.identifier.isiWOS:000232847800018-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYung, S=22636568800en_US
dc.identifier.scopusauthoridTsang, RCW=36808555100en_US
dc.identifier.scopusauthoridSun, Y=7406430327en_US
dc.identifier.scopusauthoridLeung, JKH=36857921300en_US
dc.identifier.scopusauthoridChan, TM=7402687700en_US

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