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Characterization of cecal gene expression in a differentially susceptible mouse model of bacterial-induced inflammatory bowel disease.

Abstract：

BACKGROUND:A/JCr mice develop typhlitis in response to Helicobacter hepaticus infection, whereas C57BL/6 mice coexist with this bacterium in a "commensal" relationship and do not develop disease even during prolonged colonization. METHODS:To determine mechanisms that control this balance between responsiveness and nonresponsiveness, the mucosal response of A/JCr and C57BL/6 mice to acute H. hepaticus colonization was evaluated using genome-wide profiling. Transcription levels for a subset of gene discoveries were then evaluated longitudinally by semiquantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) to identify changes in gene expression that occur during progression from the acute to chronic phase of colonization. To determine whether chronic mucosal inflammation in A/JCr mice was mediated through a Th1 mechanism, as was inferred from the gene expression data, mice with typhlitis were treated with neutralizing antibody targeting IL-12/23p40 or IFN-gamma and the response to treatment was determined by cecal lesion severity and transcription of disease-related genes. RESULTS:A/JCr mice had a biphasic expression of proinflammatory genes that corresponded with the acute and chronic phases of disease. In contrast, C57BL/6 mice exhibited a less robust acute transcriptional response that waned by day 30 postinoculation. Sustained upregulation of proinflammatory signals and responsiveness to anti-IL-12/23p40 and anti-IFN-gamma antibody suggests that inflammation in A/JCr mice was mediated through a Th1 mechanism. Prolonged upregulation of SOCS3 during the acute response to colonization suggests that C57BL/6 mice maintain mucosal homeostasis, at least in part by attenuating responsiveness to cytokine signaling. CONCLUSIONS:Collectively, these findings provide a foundation for understanding the immunological mechanisms that confer resistance or susceptibility to H. hepaticus-induced typhlitis.

journal_name

Inflamm Bowel Dis

journal_title

Inflammatory bowel diseases

authors

Myles MH,Dieckgraefe BK,Criley JM,Franklin CL

doi

10.1002/ibd.20138

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

822-36

issue

eissn

1078-0998

issn

1536-4844

journal_volume

pub_type

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Characterization of cecal gene expression in a differentially susceptible mouse model of bacterial-induced inflammatory bowel disease.