Analysis of Gene Expression in Ceca ofHelicobacter hepaticus-Infected A/JCr Mice before and after Development of Typhlitis

Abstract

The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. The causes of these diseases remain unknown; however, prevailing theories suggest that chronic intestinal inflammation results from a dysregulated immune response to ubiquitous bacterial antigens. While a substantial body of data has been amassed describing the role of the adaptive immune system in perpetuating and sustaining inflammation, very little is known about the early signals, prior to the development of inflammation, that initiate and direct the abnormal immune response. To this end, we characterized the gene expression profile of A/JCr mice with Helicobacter hepaticus-induced typhlitis at month 1 of infection, prior to the onset of histologic disease, and month 3 of infection, after chronic inflammation is fully established. Analysis of the gene expression in ceca of H. hepaticus infected mice revealed 25 up-regulated and 3 down-regulated genes in the month-1 postinoculation group and 31 up-regulated and 2 down-regulated genes in the month-3 postinoculation group. Among these was a subset of immune-related genes, including interferon-inducible protein 10, monokine induced by gamma interferon, macrophage-induced protein 1 alpha, and serum amyloid A1. Semiquantitative real-time reverse transcriptase PCR confirmed the increased expression levels of these genes, as well as elevated expression of gamma interferon. To our knowledge, this is the first report profiling cecal gene expression in H. hepaticus-infected A/JCr mice. The findings of altered gene expression prior to the development of any features of pathology and the ensuing chronic disease course make this an attractive model for studying early host response to microbe-induced inflammatory bowel disease.

Prevalence of Helicobacter hepaticus, Murine Norovirus, and Pneumocystis carinii and Eradication Efficacy of Cross-Fostering in Genetically Engineered Mice

“…Moreover, this pathogen may cause intestinal disease and gallstones in immunocompetent mice such as C57BL/6 and A/JCr [19,21,23,35]. Mice are usually infected with H. hepaticus through fecal-oral contact, and transplacental infection can occur in immunodeficient mice [18].…”

Bacteria-Induced Intestinal Cancer in Mice with DisruptedGpx1andGpx2Genes

“…© 2004 American Association for Cancer cancerres.aacrjournals.org Downloaded from 56). Colonization with H. hepaticus in A/JCr mice induces oxidative DNA damage in the liver and the expression of a subset of immunerelated genes, including ␥-IFN in cecal epithelium (57)(58)(59). H. pylori induces H 2 O 2 production and cyclooxygenase-2 expression in gastric epithelial cells (60).…”

Apolipoprotein H, an Acute Phase Protein, a Performing Tool for Ultra-Sensitive Detection and Isolation of Microorganisms from Different Origins

“…However, the expression of the acute phase protein, ApoH, sometimes is upregulated and sometimes is down regulated, reflecting its pleiotropic functions Then, it become difficult to classify this APP as positive or negative. Indeed, divers data are sometime contradictory such as the observation of ApoH reduction in CSF during cerebral malaria (Agar et al, 2011) and the increase of ApoH in several other infectious diseases (Gast et al, 2006;Myles et al, 2003;van Hemert et al, 2006). Due to different results presented here, ApoH can be considered as one of the major elements of the first line of the innate immune response regulating homeostasis.…”

“…In a rare clinical case showing that a purpura fulminans phenomenon following an infection with Haemophilus influenzae in an adult was associated to a drastic elevation of the ApoH plasma concentration (Gast et al, 2006). A gene expression study performed on Helicobacter hepaticus-infected mice showed an increased expression of the gene of ApoH three months after infection, once a chronic inflammation was established (Myles et al, 2003). The infection of chickens with Salmonella leads to high ApoH gene over-expression approximately 40-fold excess as compared with uninfected controls (van Hemert et al, 2006).…”