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Article: Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo

TitleAlbumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo
Authors
Issue Date2003
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 2003, v. 111 n. 4, p. 515-527 How to Cite?
AbstractRenal tubulointerstitial injury is characterized by inflammatory cell infiltrate; however, the stimuli for leukocyte recruitment are not fully understood. IL-8 is a potent chemokine produced by proximal tubular epithelial cells (PTECs). Whether nephrotic proteins stimulate tubular IL-8 expression remains unknown. Acute exposure of human PTECs to albumin induced IL-8 gene and protein expression time- and dose-dependently. Apical albumin predominantly stimulated basolateral IL-8 secretion. Electrophoretic mobility shift assay demonstrated nuclear translocation of NF-κB, and the p65/p50 subunits were activated. NF-κB activation and IL-8 secretion were attenuated by the NF-κB inhibitors pyrrolidine dithiocarbamate and cell-permeable peptide. Albumin upregulated intracellular reactive oxygen species (ROS) generation, while exogenous H2O2 stimulated NF-κB translocation and IL-8 secretion. Albumin-induced ROS generation, NF-κB activation, and IL-8 secretion were endocytosis- and PKC-dependent as these downstream events were abrogated by the PI3K inhibitors LY294002 and wortmannin, and the PKC inhibitors GF109203X and staurosporin, respectively. In vivo, IL-8 mRNA expression was localized by in situ hybridization to the proximal tubules in nephrotic kidney tissues. The intensity of IL-8 immunostaining was higher in nephrotic than non-nephrotic subjects. In conclusion, albumin is a strong stimulus for tubular IL-8 expression, which occurs via NF-κB-dependent pathways through PKC activation and ROS generation.
Persistent Identifierhttp://hdl.handle.net/10722/43099
ISSN
2023 Impact Factor: 13.3
2023 SCImago Journal Rankings: 4.833
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, Sen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorAbe, Ken_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorChan, TMen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2007-03-23T04:38:49Z-
dc.date.available2007-03-23T04:38:49Z-
dc.date.issued2003en_HK
dc.identifier.citationJournal Of Clinical Investigation, 2003, v. 111 n. 4, p. 515-527en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/43099-
dc.description.abstractRenal tubulointerstitial injury is characterized by inflammatory cell infiltrate; however, the stimuli for leukocyte recruitment are not fully understood. IL-8 is a potent chemokine produced by proximal tubular epithelial cells (PTECs). Whether nephrotic proteins stimulate tubular IL-8 expression remains unknown. Acute exposure of human PTECs to albumin induced IL-8 gene and protein expression time- and dose-dependently. Apical albumin predominantly stimulated basolateral IL-8 secretion. Electrophoretic mobility shift assay demonstrated nuclear translocation of NF-κB, and the p65/p50 subunits were activated. NF-κB activation and IL-8 secretion were attenuated by the NF-κB inhibitors pyrrolidine dithiocarbamate and cell-permeable peptide. Albumin upregulated intracellular reactive oxygen species (ROS) generation, while exogenous H2O2 stimulated NF-κB translocation and IL-8 secretion. Albumin-induced ROS generation, NF-κB activation, and IL-8 secretion were endocytosis- and PKC-dependent as these downstream events were abrogated by the PI3K inhibitors LY294002 and wortmannin, and the PKC inhibitors GF109203X and staurosporin, respectively. In vivo, IL-8 mRNA expression was localized by in situ hybridization to the proximal tubules in nephrotic kidney tissues. The intensity of IL-8 immunostaining was higher in nephrotic than non-nephrotic subjects. In conclusion, albumin is a strong stimulus for tubular IL-8 expression, which occurs via NF-κB-dependent pathways through PKC activation and ROS generation.en_HK
dc.format.extent2904122 bytes-
dc.format.extent26624 bytes-
dc.format.extent64634 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/msword-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.relation.ispartofJournal of Clinical Investigationen_HK
dc.subject.mesh1-phosphatidylinositol 3-kinase - antagonists & inhibitors - metabolismen_HK
dc.subject.meshInterleukin-8 - biosynthesis - geneticsen_HK
dc.subject.meshKidney tubules, proximal - drug effects - immunology - injuries - metabolismen_HK
dc.subject.meshNf-kappa b - antagonists & inhibitors - metabolismen_HK
dc.subject.meshReactive oxygen species - metabolismen_HK
dc.titleAlbumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivoen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=111&issue=4&spage=515&epage=527&date=2003&atitle=Albumin+stimulates+interleukin-8+expression+in+proximal+tubular+epithelial+cells+in+vitro+and+in+vivoen_HK
dc.identifier.emailTang, S: scwtang@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailChan, TM: dtmchan@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityTang, S=rp00480en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1172/JCI200316079en_HK
dc.identifier.pmid12588890-
dc.identifier.pmcidPMC151921-
dc.identifier.scopuseid_2-s2.0-0037324549en_HK
dc.identifier.hkuros79060-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037324549&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume111en_HK
dc.identifier.issue4en_HK
dc.identifier.spage515en_HK
dc.identifier.epage527en_HK
dc.identifier.isiWOS:000181050200014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, S=7403437082en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridAbe, K=35414379200en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridChan, LYY=8108378300en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.issnl0021-9738-

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