セッション情報 |
Best Poster Award(Upper GI)
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タイトル |
IF-BP1-2 Assessment of Toll Like Receptor Activation by H. pylori Lipopolysaccharide
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演者 |
Georgina L. Hold(Division of Applied MedicineInstitute of Medical SciencesUniversity of AberdeenUK) |
共同演者 |
Susan H. Berry(Division of Applied MedicineInstitute of Medical SciencesUniversity of AberdeenUK), Emad M. El-Omar(Division of Applied MedicineInstitute of Medical SciencesUniversity of AberdeenUK) |
抄録 |
Introduction : H. pylori lipopolysaccharide (LPS) recognition by the host is poorly understood with conflict-ing evidence as to whether TLR2 or TLR4 is involved. H. pylori LPS is a mixture of hexa-acylated andtetra-acylated species. However there is no evidence to indicate which form activates TLR signalling.Aim : To determine whether TLR2 or TLR4 is activated by H. pylori LPS.Methods : H. pylori LPS from clinical and laboratory isolates was assessed for structural changes. A mono-cyte/LPS challenge.system was used to assess TLR gene expression and pro-inflammatory cytokine pro-duction. ln silico modelling of the orientations adopted by H. pylori LPS and their impact on TLR receptor. complex interactions were assessed.Results : H. pylori LPS from laboratory and clinical strains were shown to have compositional differenceswith hexa-acylated LPS absent from laboratory strains. Assessment of genes involved in TLR signallingindicated that H. pylori LPS induced TLR4 specific sigrialling similar to E cok’ LPS and significantly differ-ent to purified TLR2 ligand. Comparison of standard preparation and ultra-purified LPS demonstrated en-hanced inflammatory responses with unpurified preparations. ln silico docking analysis indicated thatboth H. pylori LPS species were able to dock with the activated TLR4/MD2 crystal structure but notwith TLR2.Conclusions : ll. pylori LPS activates TLR4 sigiialling with no experimental evidence to indicate TLR2 in-volvement. The magnitude of the TLR4 response is less than for E. coli and this is confirmed by the evi-dence generated from docking studies. These studies strongly suggest that TLR4-mediated immune re-sponses are important in H. pylori infection. |
索引用語 |
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