Abstract:
BACKGROUND:The early molecular changes preceding the onset of mucosal inflammation in colitis and their temporal relationship with gut permeability remain poorly defined. This study investigated functional and transcriptomic changes in mdr1a(-/-) mice lacking the intestinal transporter P-glycoprotein, which develop colitis spontaneously when exposed to normal enteric flora. METHODS:Mdr1a(-/-) mice were housed in specific pathogen-free conditions to slow colitis development and compared to congenic controls. Mucosal permeability and cytokine secretion were analyzed in ex vivo colon. Gene expression in colonic mucosal and epithelial preparations was analyzed by microarray and qPCR. Colonocyte responsiveness to bacterial antigens was measured in short-term culture. RESULTS:Colon from 4-5-week-old, disease-free mdr1a(-/-) mice was histologically normal with no evidence of increased permeability compared to controls. However, these tissues display a distinctive pattern of gene expression involving significant changes in a small number of genes. The majority of upregulated genes were associated with bacterial recognition and the ubiquitin-proteasome system and were gamma-interferon (IFN-gamma) responsive. Expression of the antiinflammatory factor pancreatitis-associated protein (PAP) and the related gene RegIIIgamma were markedly reduced. Colonocytes from 4-5-week mdr1a(-/-) exhibit similar transcriptomic changes, accompanied by higher basal chemokine secretion and increased responsiveness to LPS. Significant increases in colonic permeability were associated with older (12-16-week) mdr1a(-/-) mice displaying molecular and functional evidence of active inflammation. CONCLUSIONS:These studies show that early epithelial changes associated with altered responsiveness to bacteria precede increased permeability and mucosal inflammation in this model of colitis, highlighting the importance of P-glycoprotein in regulating interactions with the commensal microflora.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Collett A,Higgs NB,Gironella M,Zeef LA,Hayes A,Salmo E,Haboubi N,Iovanna JL,Carlson GL,Warhurst Gdoi
10.1002/ibd.20375subject
Has Abstractpub_date
2008-05-01 00:00:00pages
620-31issue
5eissn
1078-0998issn
1536-4844journal_volume
14pub_type
杂志文章abstract::Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200005000-00007
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journal_title:Inflammatory bowel diseases
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doi:10.1002/ibd.21317
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doi:10.1002/ibd.21887
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318280b11a
更新日期:2013-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21772
更新日期:2012-02-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz280
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izx063
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000581
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000218762.61217.4a
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000437044.43961.00
更新日期:2013-11-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20423
更新日期:2008-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21072
更新日期:2010-03-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000577
更新日期:2016-01-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.21896
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Many patients with Crohn's disease (CD) are treated with medications, including steroids, immunomodulators, and anti-tumor necrosis factor alpha (anti-TNF-α) agents, at the time of surgery. This study evaluated the effects of these medications on postoperative complications in CD patients. METHODS:This retr...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz010
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-199808000-00003
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been establi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20042
更新日期:2007-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy049
更新日期:2018-06-08 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000894
更新日期:2016-10-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy032
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000524
更新日期:2015-11-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2018-03-19 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz196
更新日期:2020-04-11 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1002/ibd.21233
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:Genetic susceptibility may play a more important role in the etiology of early-onset inflammatory bowel disease (IBD) than in late-onset IBD, and therefore pediatric-onset IBD patients can be expected to have a higher frequency of gene mutations. We aimed to determine genotypes and phenotypes of patients wit...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20171
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21537
更新日期:2011-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200002000-00009
更新日期:2000-02-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz054
更新日期:2019-09-18 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2018-03-19 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000183423.38037.f3
更新日期:2005-11-01 00:00:00