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Conference Paper: Anti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cells

TitleAnti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cells
Authors
Issue Date2005
PublisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEP
Citation
The 3rd World Congress of Nephrology 2005, Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277 How to Cite?
AbstractThere is limited data on the pathogenesis of tubulo-interstitial lesions in lupus nephritis. In this study we investigated the effect of human anti-DNA antibodies on IL-6 synthesis and cellular functions in proximal renal tubular epithelial cells (PTEC). PTEC were isolated from renal cortical tissue by differential sieving and digestion with collagenase. Paired polyclonal anti-DNA antibodies were isolated from 15 lupus nephritis patients during active disease and remission using DNA-cellulose affinity chromatography. Cell morphology was assessed by phase contrast microscopy, and cell proliferation and viability by MTT assay and lactate dehydrogenase release respectively. IL-6, IL-1beta, and TNF-alpha were determined in culture supernatants using commercial ELISAs. Incubation of PTEC with anti-DNA antibodies (10 micrograms IgG/ml) for time periods up to 24 h induced IL-6 secretion in a time-dependent manner (0.5 +/- 0.1, 8.0 +/- 3.1, and 12.4 +/- 4.7 ng/microgram cellular protein for control IgG, anti-DNA antibodies during inactive disease, and anti-DNA antibodies during active disease respectively, p 0.01 compared to control), which was dependent on de novo mRNA and protein synthesis. Induction of IL-6 secretion was accompanied by alterations in cell morphology, proliferation (p 0.05), and viability (p 0.05), as well as increased secretion of IL-1beta (p 0.05) and TNF-alpha (p 0.05). IL-6 induction by anti-DNA correlated with circulating anti-DNA antibody levels and their binding to cultured PTEC (Spearman r = 0.561 and 0.576 respectively, p 0.001 for both). Data from inhibition experiments using neutralizing antibodies to IL-6 and TNF-alpha, and IL-1 receptor antagonist showed that during active disease IL-6, IL-1beta, and TNF-alpha interacted synergistically with anti-DNA antibodies to induce PTEC IL-6 secretion, but TNF-alpha was not involved in such induction during remission. Our data demonstrate that anti-DNA antibodies from patients with lupus nephritis can induce IL-6 production in PTEC, through distinct mechanisms that vary according to disease activity.
Persistent Identifierhttp://hdl.handle.net/10722/101179
ISSN
2015 Impact Factor: 1.796
2015 SCImago Journal Rankings: 0.894

 

DC FieldValueLanguage
dc.contributor.authorYung, SSYen_HK
dc.contributor.authorTsang, RCWen_HK
dc.contributor.authorLeung, JKHen_HK
dc.contributor.authorChan, DTMen_HK
dc.date.accessioned2010-09-25T19:39:06Z-
dc.date.available2010-09-25T19:39:06Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 3rd World Congress of Nephrology 2005, Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277en_HK
dc.identifier.issn1320-5358en_HK
dc.identifier.urihttp://hdl.handle.net/10722/101179-
dc.description.abstractThere is limited data on the pathogenesis of tubulo-interstitial lesions in lupus nephritis. In this study we investigated the effect of human anti-DNA antibodies on IL-6 synthesis and cellular functions in proximal renal tubular epithelial cells (PTEC). PTEC were isolated from renal cortical tissue by differential sieving and digestion with collagenase. Paired polyclonal anti-DNA antibodies were isolated from 15 lupus nephritis patients during active disease and remission using DNA-cellulose affinity chromatography. Cell morphology was assessed by phase contrast microscopy, and cell proliferation and viability by MTT assay and lactate dehydrogenase release respectively. IL-6, IL-1beta, and TNF-alpha were determined in culture supernatants using commercial ELISAs. Incubation of PTEC with anti-DNA antibodies (10 micrograms IgG/ml) for time periods up to 24 h induced IL-6 secretion in a time-dependent manner (0.5 +/- 0.1, 8.0 +/- 3.1, and 12.4 +/- 4.7 ng/microgram cellular protein for control IgG, anti-DNA antibodies during inactive disease, and anti-DNA antibodies during active disease respectively, p 0.01 compared to control), which was dependent on de novo mRNA and protein synthesis. Induction of IL-6 secretion was accompanied by alterations in cell morphology, proliferation (p 0.05), and viability (p 0.05), as well as increased secretion of IL-1beta (p 0.05) and TNF-alpha (p 0.05). IL-6 induction by anti-DNA correlated with circulating anti-DNA antibody levels and their binding to cultured PTEC (Spearman r = 0.561 and 0.576 respectively, p 0.001 for both). Data from inhibition experiments using neutralizing antibodies to IL-6 and TNF-alpha, and IL-1 receptor antagonist showed that during active disease IL-6, IL-1beta, and TNF-alpha interacted synergistically with anti-DNA antibodies to induce PTEC IL-6 secretion, but TNF-alpha was not involved in such induction during remission. Our data demonstrate that anti-DNA antibodies from patients with lupus nephritis can induce IL-6 production in PTEC, through distinct mechanisms that vary according to disease activity.-
dc.languageengen_HK
dc.publisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEPen_HK
dc.relation.ispartofNephrologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.titleAnti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYung, SSY: ssyyung@hku.hken_HK
dc.identifier.emailTsang, RCW: rcwtsang@hkucc.hku.hken_HK
dc.identifier.emailChan, DTM: dtmchan@hku.hk-
dc.identifier.authorityYung, SSY=rp00455en_HK
dc.identifier.authorityChan, DTM=rp00394en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1797.2005.00421.x-
dc.identifier.hkuros105350en_HK
dc.identifier.volume10en_HK
dc.identifier.issueS1-
dc.identifier.spageA277en_HK
dc.identifier.epageA277-
dc.publisher.placeAustralia-
dc.description.otherThe 3rd World Congress of Nephrology 2005, Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277-

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