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Article: LPS-induced up-regulation of TGF-β receptor 1 is associated with TNF-α expression in human monocyte-derived macrophages

TitleLPS-induced up-regulation of TGF-β receptor 1 is associated with TNF-α expression in human monocyte-derived macrophages
Authors
KeywordsALK5
Inflammation
Septic shock
Issue Date2008
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/
Citation
Journal Of Leukocyte Biology, 2008, v. 83 n. 5, p. 1165-1173 How to Cite?
AbstractThe immunosuppressive activity of TGF-β-mediated signaling is well documented, but in contrast, its ability to promote proinflammatory responses is less clear. In this study, we report that blockade of TGF-β signaling by a specific inhibitor of the TGF-β receptor I [activin receptor-like kinase 5 (ALK5)] SB431542 significantly reduces the production of TNF-α, a key proinflammatory cytokine, by LPS-stimulated human monocyte-derived macrophages. ALK5 protein was only detectable after LPS stimulation, and the failure of treatment with SB431542 to alter TNF-α mRNA expression indicates that regulation is post-transcriptional. The additive effect of blocking TGF-β and p38 MAPK signaling on reducing TNF-α but not IL-6 production suggests that there is selectivity in pathway signaling. SB431542 had similar inhibitory effects on TNF-α production by human monocytes and endothelial cells as well as macrophages. Furthermore, treatment with SB431542 reduced plasma TNF-α levels and tissue damage and thereby, prevented the lethal effects of LPS in a mouse model of septic shock. Our data demonstrate a direct effect of TGF-β signaling via ALK5 on the regulation of TNF-α synthesis. © Society for Leukocyte Biology.
Persistent Identifierhttp://hdl.handle.net/10722/92193
ISSN
2015 Impact Factor: 4.165
2015 SCImago Journal Rankings: 2.463
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Yen_HK
dc.contributor.authorKam, CSKen_HK
dc.contributor.authorFeng, QLen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-17T10:38:49Z-
dc.date.available2010-09-17T10:38:49Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Leukocyte Biology, 2008, v. 83 n. 5, p. 1165-1173en_HK
dc.identifier.issn0741-5400en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92193-
dc.description.abstractThe immunosuppressive activity of TGF-β-mediated signaling is well documented, but in contrast, its ability to promote proinflammatory responses is less clear. In this study, we report that blockade of TGF-β signaling by a specific inhibitor of the TGF-β receptor I [activin receptor-like kinase 5 (ALK5)] SB431542 significantly reduces the production of TNF-α, a key proinflammatory cytokine, by LPS-stimulated human monocyte-derived macrophages. ALK5 protein was only detectable after LPS stimulation, and the failure of treatment with SB431542 to alter TNF-α mRNA expression indicates that regulation is post-transcriptional. The additive effect of blocking TGF-β and p38 MAPK signaling on reducing TNF-α but not IL-6 production suggests that there is selectivity in pathway signaling. SB431542 had similar inhibitory effects on TNF-α production by human monocytes and endothelial cells as well as macrophages. Furthermore, treatment with SB431542 reduced plasma TNF-α levels and tissue damage and thereby, prevented the lethal effects of LPS in a mouse model of septic shock. Our data demonstrate a direct effect of TGF-β signaling via ALK5 on the regulation of TNF-α synthesis. © Society for Leukocyte Biology.en_HK
dc.languageengen_HK
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/en_HK
dc.relation.ispartofJournal of Leukocyte Biologyen_HK
dc.subjectALK5en_HK
dc.subjectInflammationen_HK
dc.subjectSeptic shocken_HK
dc.titleLPS-induced up-regulation of TGF-β receptor 1 is associated with TNF-α expression in human monocyte-derived macrophagesen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, Y:ychenc@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH:vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH:paultam@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp01318en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1189/jlb.0807521en_HK
dc.identifier.pmid18252868-
dc.identifier.scopuseid_2-s2.0-46949085159en_HK
dc.identifier.hkuros142261-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-46949085159&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume83en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1165en_HK
dc.identifier.epage1173en_HK
dc.identifier.isiWOS:000258019500011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, Y=36463185300en_HK
dc.identifier.scopusauthoridKam, CSK=24464045000en_HK
dc.identifier.scopusauthoridFeng, QL=24464375500en_HK
dc.identifier.scopusauthoridLiu, Y=25928027200en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridLamb, JR=7201524642en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.citeulike6797309-

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