セッション情報 Best Poster Award(Upper GI)

タイトル

IF-BP1-2 Assessment of Toll Like Receptor Activation by H. pylori Lipopolysaccharide

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.
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