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Conference Paper: Anti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cells
Title | Anti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cells |
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Authors | |
Issue Date | 2005 |
Publisher | Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEP |
Citation | The 3rd ISN World Congress of Nephrology (WCN 2005), Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277 How to Cite? |
Abstract | There 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 Identifier | http://hdl.handle.net/10722/101179 |
ISSN | 2023 Impact Factor: 2.4 2023 SCImago Journal Rankings: 0.641 |
DC Field | Value | Language |
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dc.contributor.author | Yung, SSY | en_HK |
dc.contributor.author | Tsang, RCW | en_HK |
dc.contributor.author | Leung, JKH | en_HK |
dc.contributor.author | Chan, DTM | en_HK |
dc.date.accessioned | 2010-09-25T19:39:06Z | - |
dc.date.available | 2010-09-25T19:39:06Z | - |
dc.date.issued | 2005 | en_HK |
dc.identifier.citation | The 3rd ISN World Congress of Nephrology (WCN 2005), Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277 | en_HK |
dc.identifier.issn | 1320-5358 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/101179 | - |
dc.description.abstract | There 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.language | eng | en_HK |
dc.publisher | Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEP | en_HK |
dc.relation.ispartof | Nephrology | en_HK |
dc.rights | The definitive version is available at www.blackwell-synergy.com | - |
dc.title | Anti-DNA antibodies from patients with lupus nephritis induce IL-6 expression in renal tubular epithelial cells | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Yung, SSY: ssyyung@hku.hk | en_HK |
dc.identifier.email | Tsang, RCW: rcwtsang@hkucc.hku.hk | en_HK |
dc.identifier.email | Chan, DTM: dtmchan@hku.hk | - |
dc.identifier.authority | Yung, SSY=rp00455 | en_HK |
dc.identifier.authority | Chan, DTM=rp00394 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1111/j.1440-1797.2005.00421.x | - |
dc.identifier.hkuros | 105350 | en_HK |
dc.identifier.volume | 10 | en_HK |
dc.identifier.issue | suppl. 1 | - |
dc.identifier.spage | A277 | en_HK |
dc.identifier.epage | A277 | - |
dc.publisher.place | Australia | - |
dc.description.other | The 3rd World Congress of Nephrology 2005, Singapore, 26-30 June 2005. In Nephrology, 2005, v. 10 n. S1, p. A277 | - |
dc.identifier.issnl | 1320-5358 | - |