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Article: Hypoxia modulates lipopolysaccharide induced TNF-α expression in murine macrophages

TitleHypoxia modulates lipopolysaccharide induced TNF-α expression in murine macrophages
Authors
KeywordsHIF-1α
Hypoxia
Lipopolysaccharide
Macrophages
p38 MAPK
SB203580
TNF-α
Issue Date2008
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcr
Citation
Experimental Cell Research, 2008, v. 314 n. 6, p. 1327-1336 How to Cite?
AbstractThe pro-inflammatory activity of Tumor necrosis factor-alpha (TNF-α) together with tissue hypoxia determine the clinical outcome in sepsis and septic shock. p38 MAPKinase is the primary intracellular signaling pathway that regulates lipopolysaccharide (LPS)-induced TNF-α biosynthesis, however, the effect of hypoxia on LPS mediated activation of p38 is not known. Here we report that SB203580, a specific p38 MAPK inhibitor, which completely abolished LPS-induced TNF-α expression by the mouse macrophage cell RAW264.7 in normoxic conditions, lost the inhibitory effect in hypoxic conditions. Hypoxia did not modulate expression of p38 MAPK, but increased that of p-MK2, a downstream target of p38 MAPK. In LPS induced endotoxemia mice model SB203580 had no inhibitory effect on the serum levels of TNF-α. Furthermore, hypoxia inducible factor-1alpha (HIF-1α) was detected in vivo after LPS administration but its expression was not affected by SB203580. Our data indicate that LPS induced p38 MAPK activation was enhanced by hypoxia and consequently increased TNF-α secretion. Furthermore, the induction of HIF-1α in mice with endotoxemia suggested a synergistic effect on p38 mediated TNF-α expression. These findings provide new insights on the pathophysiological effects of hypoxia in sepsis and septic shock. © 2008 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/92250
ISSN
2015 Impact Factor: 3.378
2015 SCImago Journal Rankings: 1.900
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Fen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorChen, Yen_HK
dc.date.accessioned2010-09-17T10:40:30Z-
dc.date.available2010-09-17T10:40:30Z-
dc.date.issued2008en_HK
dc.identifier.citationExperimental Cell Research, 2008, v. 314 n. 6, p. 1327-1336en_HK
dc.identifier.issn0014-4827en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92250-
dc.description.abstractThe pro-inflammatory activity of Tumor necrosis factor-alpha (TNF-α) together with tissue hypoxia determine the clinical outcome in sepsis and septic shock. p38 MAPKinase is the primary intracellular signaling pathway that regulates lipopolysaccharide (LPS)-induced TNF-α biosynthesis, however, the effect of hypoxia on LPS mediated activation of p38 is not known. Here we report that SB203580, a specific p38 MAPK inhibitor, which completely abolished LPS-induced TNF-α expression by the mouse macrophage cell RAW264.7 in normoxic conditions, lost the inhibitory effect in hypoxic conditions. Hypoxia did not modulate expression of p38 MAPK, but increased that of p-MK2, a downstream target of p38 MAPK. In LPS induced endotoxemia mice model SB203580 had no inhibitory effect on the serum levels of TNF-α. Furthermore, hypoxia inducible factor-1alpha (HIF-1α) was detected in vivo after LPS administration but its expression was not affected by SB203580. Our data indicate that LPS induced p38 MAPK activation was enhanced by hypoxia and consequently increased TNF-α secretion. Furthermore, the induction of HIF-1α in mice with endotoxemia suggested a synergistic effect on p38 mediated TNF-α expression. These findings provide new insights on the pathophysiological effects of hypoxia in sepsis and septic shock. © 2008 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcren_HK
dc.relation.ispartofExperimental Cell Researchen_HK
dc.subjectHIF-1αen_HK
dc.subjectHypoxiaen_HK
dc.subjectLipopolysaccharide-
dc.subjectMacrophages-
dc.subjectp38 MAPK-
dc.subjectSB203580-
dc.subjectTNF-α-
dc.titleHypoxia modulates lipopolysaccharide induced TNF-α expression in murine macrophagesen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, Y:ychenc@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp1318en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.yexcr.2008.01.007en_HK
dc.identifier.pmid18255061-
dc.identifier.scopuseid_2-s2.0-40049104711en_HK
dc.identifier.hkuros141334-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-40049104711&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume314en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1327en_HK
dc.identifier.epage1336en_HK
dc.identifier.isiWOS:000254612700012-
dc.identifier.scopusauthoridLiu, F=36067266700-
dc.identifier.scopusauthoridLiu, Y=25928027200-
dc.identifier.scopusauthoridLui, VCH=7004231344-
dc.identifier.scopusauthoridLamb, JR=7201524642-
dc.identifier.scopusauthoridTam, PKH=7202539421-
dc.identifier.scopusauthoridChen, Y=7601428288-

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