File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Mycophenolic acid ameliorates anti-dsDNA antibody binding to proximal tubular epithelial cells and the subsequent induction of inflammatory and fibrotic processes

TitleMycophenolic acid ameliorates anti-dsDNA antibody binding to proximal tubular epithelial cells and the subsequent induction of inflammatory and fibrotic processes
Authors
KeywordsMedical sciences
Rheumatology
Issue Date2010
PublisherSage Publications Ltd. The Journal's web site is located at http://lup.sagepub.com
Citation
The 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115, abstract no. PO1.M.3 How to Cite?
AbstractOBJECTIVES: Severe active proliferative lupus nephritis is associated with inflammation in the renal parenchyma and elevated levels of anti-dsDNA antibodies. Up to 70% of patients with lupus nephritis show immune deposits along the tubular basement membrane, and the severity of tubulo-interstitial inflammation and injury correlate with long-term renal prognosis. We investigated the interaction between polyclonal anti-dsDNA antibodies isolated from patients with lupus nephritis and cultured proximal tubular epithelial cells (PTEC), and the effect of mycophenolic acid (MPA). METHODS: Human polyclonal anti-dsDNA antibodies were isolated from patients with lupus nephritis using affinity chromatography. Their interaction with PTEC in the presence or absence of MPA (5μg/ml) was assessed by flow cytometry, cellular ELISA and immunohistochemistry. Induction of IL-6, IL-8, MCP-1 and fibronectin was assessed by commercial ELISAs, and MAPK activation by Western blot analysis. RESULTS: Anti-dsDNA antibodies bound directly to PTEC surface without the need for bridging chromatin material, and were then internalized, in a time- and temperature-dependent manner, into the cytoplasmic and nuclear compartments. Binding of anti-dsDNA antibodies to PTEC induced cell proliferation, IL-6 secretion through JNK activation, and MCP-1 through p38 MAPK activation. Activation of ERK, p38 MAPK and JNK contributed to the induction of IL-8 and fibronectin secretion by anti-dsDNA antibodies (p<0.05 for all compared to control IgG). MPA inhibited anti-dsDNA antibody binding to PTEC, its induction of cell proliferation, activation of ERK, p38 MAPK and JNK, and IL-6, IL-8, MCP-1 and fibronectin secretion. CONCLUSIONS: Our data demonstrate the significance of anti-dsDNA antibody interaction with PTEC in the pathogenesis of tubulo-interstitial inflammation and fibrosis in lupus nephritis, and the therapeutic effect of MPA in this regard.
DescriptionPoster Presentations - PO1M Pathogenesis: PO1.M.3
Persistent Identifierhttp://hdl.handle.net/10722/126444
ISSN
2015 Impact Factor: 2.118
2015 SCImago Journal Rankings: 0.878

 

DC FieldValueLanguage
dc.contributor.authorYung, Sen_HK
dc.contributor.authorNg, YCCen_HK
dc.contributor.authorChan, DTMen_HK
dc.date.accessioned2010-10-31T12:28:57Z-
dc.date.available2010-10-31T12:28:57Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115, abstract no. PO1.M.3en_HK
dc.identifier.issn0961-2033-
dc.identifier.urihttp://hdl.handle.net/10722/126444-
dc.descriptionPoster Presentations - PO1M Pathogenesis: PO1.M.3-
dc.description.abstractOBJECTIVES: Severe active proliferative lupus nephritis is associated with inflammation in the renal parenchyma and elevated levels of anti-dsDNA antibodies. Up to 70% of patients with lupus nephritis show immune deposits along the tubular basement membrane, and the severity of tubulo-interstitial inflammation and injury correlate with long-term renal prognosis. We investigated the interaction between polyclonal anti-dsDNA antibodies isolated from patients with lupus nephritis and cultured proximal tubular epithelial cells (PTEC), and the effect of mycophenolic acid (MPA). METHODS: Human polyclonal anti-dsDNA antibodies were isolated from patients with lupus nephritis using affinity chromatography. Their interaction with PTEC in the presence or absence of MPA (5μg/ml) was assessed by flow cytometry, cellular ELISA and immunohistochemistry. Induction of IL-6, IL-8, MCP-1 and fibronectin was assessed by commercial ELISAs, and MAPK activation by Western blot analysis. RESULTS: Anti-dsDNA antibodies bound directly to PTEC surface without the need for bridging chromatin material, and were then internalized, in a time- and temperature-dependent manner, into the cytoplasmic and nuclear compartments. Binding of anti-dsDNA antibodies to PTEC induced cell proliferation, IL-6 secretion through JNK activation, and MCP-1 through p38 MAPK activation. Activation of ERK, p38 MAPK and JNK contributed to the induction of IL-8 and fibronectin secretion by anti-dsDNA antibodies (p<0.05 for all compared to control IgG). MPA inhibited anti-dsDNA antibody binding to PTEC, its induction of cell proliferation, activation of ERK, p38 MAPK and JNK, and IL-6, IL-8, MCP-1 and fibronectin secretion. CONCLUSIONS: Our data demonstrate the significance of anti-dsDNA antibody interaction with PTEC in the pathogenesis of tubulo-interstitial inflammation and fibrosis in lupus nephritis, and the therapeutic effect of MPA in this regard.-
dc.languageengen_HK
dc.publisherSage Publications Ltd. The Journal's web site is located at http://lup.sagepub.com-
dc.relation.ispartofLupus-
dc.rightsLupus. Copyright © Sage Publications Ltd.-
dc.subjectMedical sciences-
dc.subjectRheumatology-
dc.titleMycophenolic acid ameliorates anti-dsDNA antibody binding to proximal tubular epithelial cells and the subsequent induction of inflammatory and fibrotic processesen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0961-2033&volume=19&issue=1, suppl.&spage=115&epage=&date=2010&atitle=Mycophenolic+acid+ameliorates+anti-dsDNA+antibody+binding+to+proximal+tubular+epithelial+cells+and+the+subsequent+induction+of+inflammatory+and+fibrotic+processes-
dc.identifier.emailYung, S: ssyyung@hku.hken_HK
dc.identifier.emailChan, DTM: dtmchan@hku.hken_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.identifier.authorityChan, DTM=rp00394en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1177/09612033100190010101-
dc.identifier.pmid20511279-
dc.identifier.scopuseid_2-s2.0-77953045627-
dc.identifier.hkuros172764en_HK
dc.identifier.volume19-
dc.identifier.issue1, suppl.-
dc.identifier.spage115-
dc.identifier.epage115-
dc.description.otherThe 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115, abstract no. PO1.M.3-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats