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- Publisher Website: 10.1189/jlb.0807521
- Scopus: eid_2-s2.0-46949085159
- PMID: 18252868
- WOS: WOS:000258019500011
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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
Title | LPS-induced up-regulation of TGF-β receptor 1 is associated with TNF-α expression in human monocyte-derived macrophages |
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Authors | |
Keywords | ALK5 Inflammation Septic shock |
Issue Date | 2008 |
Publisher | Federation 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/92193 |
ISSN | 2023 Impact Factor: 3.6 2023 SCImago Journal Rankings: 1.521 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chen, Y | en_HK |
dc.contributor.author | Kam, CSK | en_HK |
dc.contributor.author | Feng, QL | en_HK |
dc.contributor.author | Liu, Y | en_HK |
dc.contributor.author | Lui, VCH | en_HK |
dc.contributor.author | Lamb, JR | en_HK |
dc.contributor.author | Tam, PKH | en_HK |
dc.date.accessioned | 2010-09-17T10:38:49Z | - |
dc.date.available | 2010-09-17T10:38:49Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Journal Of Leukocyte Biology, 2008, v. 83 n. 5, p. 1165-1173 | en_HK |
dc.identifier.issn | 0741-5400 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/92193 | - |
dc.description.abstract | The 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.language | eng | en_HK |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/ | en_HK |
dc.relation.ispartof | Journal of Leukocyte Biology | en_HK |
dc.subject | ALK5 | en_HK |
dc.subject | Inflammation | en_HK |
dc.subject | Septic shock | en_HK |
dc.title | LPS-induced up-regulation of TGF-β receptor 1 is associated with TNF-α expression in human monocyte-derived macrophages | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Chen, Y:ychenc@hkucc.hku.hk | en_HK |
dc.identifier.email | Lui, VCH:vchlui@hkucc.hku.hk | en_HK |
dc.identifier.email | Tam, PKH:paultam@hkucc.hku.hk | en_HK |
dc.identifier.authority | Chen, Y=rp01318 | en_HK |
dc.identifier.authority | Lui, VCH=rp00363 | en_HK |
dc.identifier.authority | Tam, PKH=rp00060 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1189/jlb.0807521 | en_HK |
dc.identifier.pmid | 18252868 | - |
dc.identifier.scopus | eid_2-s2.0-46949085159 | en_HK |
dc.identifier.hkuros | 142261 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-46949085159&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 83 | en_HK |
dc.identifier.issue | 5 | en_HK |
dc.identifier.spage | 1165 | en_HK |
dc.identifier.epage | 1173 | en_HK |
dc.identifier.isi | WOS:000258019500011 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Chen, Y=36463185300 | en_HK |
dc.identifier.scopusauthorid | Kam, CSK=24464045000 | en_HK |
dc.identifier.scopusauthorid | Feng, QL=24464375500 | en_HK |
dc.identifier.scopusauthorid | Liu, Y=25928027200 | en_HK |
dc.identifier.scopusauthorid | Lui, VCH=7004231344 | en_HK |
dc.identifier.scopusauthorid | Lamb, JR=7201524642 | en_HK |
dc.identifier.scopusauthorid | Tam, PKH=7202539421 | en_HK |
dc.identifier.citeulike | 6797309 | - |
dc.identifier.issnl | 0741-5400 | - |