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Conference Paper: In-vitro and in-vivo induction of interleukin-8 expression by albumin in proximal tubular epithelial cells: an extended study

TitleIn-vitro and in-vivo induction of interleukin-8 expression by albumin in proximal tubular epithelial cells: an extended study
Authors
Issue Date2003
PublisherHong Kong Medical Association. The Journal's web site is located at http://www.hkmj.org
Citation
The 8th Medical Research Conference of Department of Medicine, The University of Hong Kong, Hong Kong, 25 – 26 January 2003. In Hong Kong Medical Journal, 2003, v. 9 n. S1, p. 70 How to Cite?
AbstractIntroduction: We have previously demonstrated that albumin superinduces the expression of IL-8, a potent chemokine, in cultured human renal proximal tubular epithelial cells (PTEC). In this study, we explored the intracellular signaling mechanisms leading to heightened IL-8 production in the nephrotic mileu. Method: Human PTEC was obtained by primary culture. Endocytosis of albumin was assayed by flow cytometry. IL-8 gene and protein expression was measured by RT-PCR and ELISA, respectively. The role of NFkappaB was determined by electrophoretic mobility shift assay, and confirmed with the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), and a decoy peptide. Intracellular generation of reactive oxygen species (ROS) was detected by a specific fluorescence probe. IL-8 expression in kidney biopsies of nephrotic subjects was studied by immunohistochemistry and in-situ hybridization. Results: Receptor-mediated endocytosis of albumin by PTEC significantly induced IL-8 gene expression, which was localized by in situ hybridization to the proximal tubules in nephrotic kidney tissues. Apical albumin stimulated IL-8 secretion in both directions, with basolateral secretion predominating. Albumin activated nuclear translocation of both the p65 and p50 subunits of NF-kappaB. There was corresponding upregulation of intracellular ROS. Albumin-induced tubular IL-8 secretion was abrogated by PDTC, or the cell-permeable peptide, SN50, but not the mutant sequence, SN50M. Histologic scores, graded in an observer-blinded fashion, for IL-8 immunostaining were higher in nephrotic than non-nephrotic subjects (P = 0.039), and correlated with the magnitude of proteinuria (r2 = 0.332, b = 0.116 [95% CI, 0.029-0.203], P = 0.012). Conclusion: Albumin is a strong stimulus for tubular IL-8 expression both in vivo and in vitro, which occurs via NF-κB-dependent pathways. Our findings provide evidence that tubule-secreted IL-8 is important in the pathogenesis of tubulointerstitial inflammation in the proteinuric state. *Supported by the UDM Research Grant 00/01.
Persistent Identifierhttp://hdl.handle.net/10722/101568
ISSN
2015 Impact Factor: 0.887
2015 SCImago Journal Rankings: 0.279

 

DC FieldValueLanguage
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorAbe, Ken_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorChan, LYen_HK
dc.contributor.authorChan, DTMen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-09-25T19:54:57Z-
dc.date.available2010-09-25T19:54:57Z-
dc.date.issued2003en_HK
dc.identifier.citationThe 8th Medical Research Conference of Department of Medicine, The University of Hong Kong, Hong Kong, 25 – 26 January 2003. In Hong Kong Medical Journal, 2003, v. 9 n. S1, p. 70en_HK
dc.identifier.issn1024-2708en_HK
dc.identifier.urihttp://hdl.handle.net/10722/101568-
dc.description.abstractIntroduction: We have previously demonstrated that albumin superinduces the expression of IL-8, a potent chemokine, in cultured human renal proximal tubular epithelial cells (PTEC). In this study, we explored the intracellular signaling mechanisms leading to heightened IL-8 production in the nephrotic mileu. Method: Human PTEC was obtained by primary culture. Endocytosis of albumin was assayed by flow cytometry. IL-8 gene and protein expression was measured by RT-PCR and ELISA, respectively. The role of NFkappaB was determined by electrophoretic mobility shift assay, and confirmed with the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), and a decoy peptide. Intracellular generation of reactive oxygen species (ROS) was detected by a specific fluorescence probe. IL-8 expression in kidney biopsies of nephrotic subjects was studied by immunohistochemistry and in-situ hybridization. Results: Receptor-mediated endocytosis of albumin by PTEC significantly induced IL-8 gene expression, which was localized by in situ hybridization to the proximal tubules in nephrotic kidney tissues. Apical albumin stimulated IL-8 secretion in both directions, with basolateral secretion predominating. Albumin activated nuclear translocation of both the p65 and p50 subunits of NF-kappaB. There was corresponding upregulation of intracellular ROS. Albumin-induced tubular IL-8 secretion was abrogated by PDTC, or the cell-permeable peptide, SN50, but not the mutant sequence, SN50M. Histologic scores, graded in an observer-blinded fashion, for IL-8 immunostaining were higher in nephrotic than non-nephrotic subjects (P = 0.039), and correlated with the magnitude of proteinuria (r2 = 0.332, b = 0.116 [95% CI, 0.029-0.203], P = 0.012). Conclusion: Albumin is a strong stimulus for tubular IL-8 expression both in vivo and in vitro, which occurs via NF-κB-dependent pathways. Our findings provide evidence that tubule-secreted IL-8 is important in the pathogenesis of tubulointerstitial inflammation in the proteinuric state. *Supported by the UDM Research Grant 00/01.-
dc.languageengen_HK
dc.publisherHong Kong Medical Association. The Journal's web site is located at http://www.hkmj.orgen_HK
dc.relation.ispartofHong Kong Medical Journalen_HK
dc.rightsHong Kong Medical Journal . Copyright © Hong Kong Medical Association.en_HK
dc.titleIn-vitro and in-vivo induction of interleukin-8 expression by albumin in proximal tubular epithelial cells: an extended studyen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1024-2708&volume=9&spage=70&epage=&date=2003&atitle=In-vitro+and+in-vivo+induction+of+interleukin-8+expression+by+albumin+in+proximal+tubular+epithelial+cells:+an+extended+studyen_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailChan, DTM: dtmchan@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityChan, DTM=rp00394en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.identifier.hkuros136857en_HK
dc.identifier.volume9en_HK
dc.identifier.spage70en_HK

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