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Article: Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation

TitleHeme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation
Authors
Issue Date2004
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2004, v. 172 n. 6, p. 3553-3563 How to Cite?
AbstractHeme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-alpha-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-kappaB, a transcription factor required for TNF-alpha-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-kappaB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.
Persistent Identifierhttp://hdl.handle.net/10722/49344
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSoares, MPen_HK
dc.contributor.authorSeldon, MPen_HK
dc.contributor.authorGregoire, IPen_HK
dc.contributor.authorVassilevskaia, Ten_HK
dc.contributor.authorBerberat, POen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorTsui, TYen_HK
dc.contributor.authorBach, FHen_HK
dc.date.accessioned2008-06-12T06:39:56Z-
dc.date.available2008-06-12T06:39:56Z-
dc.date.issued2004en_HK
dc.identifier.citationJournal of Immunology, 2004, v. 172 n. 6, p. 3553-3563en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49344-
dc.description.abstractHeme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-alpha-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-kappaB, a transcription factor required for TNF-alpha-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-kappaB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.en_HK
dc.format.extent420 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (The AAI), publisher of The JI, holds the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). The AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.orgen_HK
dc.subject.meshEndothelium, Vascular - cytology - enzymology - immunology - metabolismen_HK
dc.subject.meshHeme Oxygenase (Decyclizing) - biosynthesis - genetics - physiologyen_HK
dc.subject.meshAdenoviridae - geneticsen_HK
dc.subject.meshBilirubin - pharmacologyen_HK
dc.subject.meshCarbon Monoxide - pharmacologyen_HK
dc.titleHeme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1767&volume=172&issue=6&spage=3553&epage=3563&date=2004&atitle=Heme+oxygenase-1+modulates+the+expression+of+adhesion+molecules+associated+with+endothelial+cell+activationen_HK
dc.identifier.emailTsui, TY: tytsui@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid15004156-
dc.identifier.scopuseid_2-s2.0-1542724430-
dc.identifier.hkuros89298-
dc.identifier.isiWOS:000220096000026-

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