Linked Life Data

18665050

Source:http://linkedlifedata.com/resource/pubmed/id/18665050

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-19
pubmed:abstractText
The inflammatory response after an insult may provoke further tissue damage, and the macrophage is central in this pathophysiology. Induction of heme oxygenase-1 (HO-1) attenuates postshock organ dysfunction, although the mechanism remains unclear. We hypothesized that HO-1 induction modifies the cytokine profile of LPS-stimulated macrophages. Heme oxygenase-1 was induced in murine and human macrophages with varying concentrations of a hemoglobin-based oxygen carrier (HBOC). Heme oxygenase-1 expression was analyzed by Western blotting of whole cell lysates. Macrophages were pretreated with HBOC for 4 h, then media with LPS were added for up to 24 h. The specific HO-1 inhibitor zinc protoporphyrin (ZnPP) was used to inhibit the effects of HO-1. Supernatants were analyzed for IL-6, IL-10, TNF-alpha, and monocyte chemotactic protein 1 (MCP-1) by enzyme-linked immunosorbent assay. Incubation of cells with HBOC produced a dose-dependent expression of HO-1. Heme oxygenase-1 expression decreased LPS-stimulated secretion of MCP-1, IL-6, IL-10, and TNF-alpha at both 4 and 24 h in murine and human macrophages. The addition of ZnPP to inhibit HO-1 partially restored MCP-1 and IL-6 secretion in murine macrophages. Furthermore, immunofluorescent microscopy revealed HBOC-induced HO-1 inhibited LPS-stimulated nuclear translocation of the p65 subunit of nuclear factor-kappaB. In summary, HBOC incubation of macrophages induced HO-1 expression, which reduced LPS-mediated cytokine release, and that MCP-1 and IL-6 secretion could be partially restored with ZnPP. These data encourage continued investigation into the role of HO-1 in protecting against posttraumatic organ dysfunction and the clinical potential of HBOC for HO-1 induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Blood Substitutes, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/HMOX1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Protoporphyrins, http://linkedlifedata.com/resource/pubmed/chemical/RELA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Rela protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA, http://linkedlifedata.com/resource/pubmed/chemical/zinc protoporphyrin
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1540-0514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
251-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Heme oxygenase-1 induction in macrophages by a hemoglobin-based oxygen carrier reduces endotoxin-stimulated cytokine secretion.
pubmed:affiliation
Department of Surgery, The University of Colorado Denver, Aurora, USA.
pubmed:publicationType
Journal Article