| Differential Effect of Inhibiting MD-2 and CD14 on LPS- Versus Whole E. coli Bacteria-Induced Cytokine Responses in Human Blood. | |
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MedLine Citation:
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PMID: 21948372 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Background: Sepsis Sepsis is a major world-wide medical problem with high morbidity and mortality. Gram-negative bacteria are among the most important pathogens of sepsis and their LPS LPS content is regarded to be important for the systemic inflammatory reaction. The CD14 CD14 /myeloid differentiation factor 2 (MD-2 MD-2 )/TLR4 complex plays a major role in the immune response to LPS LPS . The aim of this study was to compare the effects of inhibiting MD-2 MD-2 and CD14 CD14 on ultra-pure LPS LPS - versus whole E. coli E. coli bacteria-induced responses. Methods: Fresh human whole blood was incubated with upLPS or whole E. coli E. coli bacteria in the presence of MD-2 MD-2 or CD14 CD14 neutralizing monoclonal antibodies, or their respective controls, and/or the specific complement-inhibitor compstatin. Cytokines Cytokines were measured by a multiplex (n = 27) assay. NFκB activity was examined in cells transfected with CD14 CD14 , MD-2 MD-2 and/or Toll-like receptors. Results: LPS LPS -induced cytokine response was efficiently and equally abolished by MD-2 MD-2 and CD14 CD14 neutralization. In contrast, the response induced by whole E. coli E. coli bacteria was only modestly reduced by MD-2 MD-2 neutralization, whereas CD14 CD14 neutralization was more efficient. Combination with compstatin enhanced the effect of MD-2 MD-2 neutralization slightly. When compstatin was combined with CD14 CD14 neutralization, however, the response was virtually abolished for all cytokines, including IL-17, which was only inhibited by this combination. The MD-2 MD-2 -independent effect observed for CD14 CD14 could not be explained by TLR2 signaling. Conclusion: Inhibition of CD14 CD14 is more efficient than inhibition of MD-2 MD-2 on whole E. coli E. coli -induced cytokine response, suggesting CD14 CD14 to be a better target for intervention in Gram-negative sepsis, in particular when combined with complement inhibition. |
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Authors:
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D Christiansen; O L Brekke; J Stenvik; J D Lambris; T Espevik; T E Mollnes |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Advances in experimental medicine and biology Volume: 946 ISSN: 0065-2598 ISO Abbreviation: Adv. Exp. Med. Biol. Publication Date: 2012 |
Date Detail:
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Created Date: 2011-09-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0121103 Medline TA: Adv Exp Med Biol Country: United States |
Other Details:
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Languages: eng Pagination: 237-51 Citation Subset: IM |
Affiliation:
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Research Laboratory, Somatic Research Centre, Nordland Hospital, 8092, Bodø, Norway, Dorte.Christiansen@nlsh.no. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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