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Structural requirem...
Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications
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- Bäckhed, Fredrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Normark, S. (författare)
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- Schweda, Elke K H (författare)
- Södertörns högskola,Avdelning Naturvetenskap
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Oscarson, S. (författare)
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Richter-Dahlfors, A. (författare)
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: Microbes Infect. - 1286-4579 .- 1769-714X. ; 5:12, s. 1057-63
- Relaterad länk:
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https://gup.ub.gu.se...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cells of the mucosal lining are the first to encounter invading bacteria during infection, and as such, they have developed numerous ways of detecting microbial intruders. Recently, we showed that epithelial cells recognize lipopolysaccharide (LPS) through the CD14-Toll-like receptor (TLR)-4 complex. Here, we identify the substructures of LPS that are recognized by the TLR4 receptor complex. In contrast to lipid A, the O-antigen does not mediate an inflammatory response; rather it interferes with the lipid A recognition. An Escherichia coli strain genetically modified to express penta-acylated lipid A not only showed reduced immunogenicity, but was also found to inhibit pro-inflammatory signalling induced by wild-type E. coli (hexa-acylated lipid A) as well as LPS from other bacteria of the Enterobacteriaceae family. Furthermore, penta-acylated LPS from Pseudomonas aeruginosa acted as an antagonist to hexa-acylated E. coli LPS, as did E. coli, as shown by its inhibitory effect on IL-8 production in stimulated cells. Hypo-acylated lipid A, such as that of P. aeruginosa, is found in several species within the gut microflora as well as in several bacteria causing chronic infections. Thus, our results suggest that the composition of the microflora may be important in modulating pro-inflammatory signalling in epithelial cells under normal as well as pathologic conditions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- Cell Line
- Epithelial Cells/metabolism
- Escherichia coli/pathogenicity
- Humans
- Lipopolysaccharides/immunology/ pharmacology
- Membrane Glycoproteins/ metabolism
- Pseudomonas aeruginosa/immunology
- Receptors
- Cell Surface/genetics/ metabolism
- Signal Transduction
- Toll-Like Receptor 4
- Toll-Like Receptors
- Urinary Tract Infections/immunology/microbiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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