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Dysregulation of Human β-Defensin-2 Protein in Inflammatory Bowel Disease 英文参考文献.docVIP

Dysregulation of Human β-Defensin-2 Protein in Inflammatory Bowel Disease 英文参考文献.doc

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Dysregulation of Human β-Defensin-2 Protein in Inflammatory Bowel Disease 英文参考文献

DysregulationofHumanb-Defensin-2Proteinin InflammatoryBowelDisease MarianC.Aldhous*,ColinL.Noble,JackSatsangi Gastrointestinal Unit, School of Clinical and Molecular Medicine, University of Edinburgh, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh,Scotland,UnitedKingdom Abstract Background:Humanb-defensin-2(HBD2)isanantimicrobialpeptideimplicatedinthepathogenesisofinflammatorybowel disease (IBD). Low copy number and concomitant low mRNA expression of the HBD2 gene have been implicated in susceptibilitytocolonicCrohn’sDisease(CD).WeinvestigatedthecolonicdistributionofHBD2mRNAexpression,andthe contributionsofgeneticandenvironmentalfactorsonHBD2proteinproduction. Methodology/PrincipalFindings:WeexaminedHBD2mRNAexpressionatthreecoloniclocationsbymicroarrayanalysisof biopsies from 151 patients (53 CD, 67 ulcerative colitis [UC], 31 controls). We investigated environmental and genetic influencesonHBD2proteinproductionusingexvivoculturedsigmoidcolonbiopsiesfrom69patients(22CD,26UC,21 controls) stimulated with lipopolysaccharide (LPS) and/or nicotine for 24hours. HBD2 and cytokines were measured in culturesupernatants.UsingDNAsamplesfromthesepatients,regionsintheHBD2genepromoterweresequencedforNF- kB binding-sites and HBD2 gene copy number was determined. HBD2 mRNA expression was highest in inflamed (vs. uninflamed p=0.0122) ascending colon in CD and in inflamed (vs. uninflamed p,0.0001) sigmoid colon in UC. HBD2 proteinproductionwasincreasedininflamedUCbiopsies(p=0.0078).TherewasnodifferenceinHBD2proteinproduction from unstimulated biopsies of CD, UC and controls. LPS-induced HBD2 production was significantly increased in CD (p=0.0375)butnotUC(p=0.2017);thisLPS-inducedresponsewasaugmentedbynicotineinUC(p=0.0308)butnotCD (p=0.6872). Nicotine alone did not affect HBD2 production. HBD2 production correlated with IL8 production in UC (p,0.001)andwithIL10inCD(p,0.05).VariationsintheHBD2promoterandHBD2genecopynumberdidnotaffectHBD2 production

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