TITLE

HELICOBACTER PYLORI INFECTION IN MONGOLIAN GERBILS INDUCES A TH1 GASTRIC MUCOSAL RESPONSE

AUTHOR(S)
Aboshkiwa, M.A.; Jeremy, A.H.T.; Court, M.; Dixon, M.F.; Robinson, P.A.; Crabtree, J.E.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA52
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: Chronic H pylori infection in Mongolian gerbils has been demonstrated to result in gastric cancer. The gastric mucosal inflammatory and immune response to infection has not been characterised. The aims of this study were to identify transcripts for gerbil cytokines and to examine the gastric cytokine responses to chronic H pylori infection. Methods: Female Mongolian gerbils were orally challenged three times with H pylori SS1 strain. Infected animals (n = 15) plus controls (n = 17) were sacrificed at 4, 12, and 36 weeks post-infection (p.i.). Infection was confirmed histologically and by culture. Gastric mucosa was snap frozen for analysis of cytokine transcripts by RT-PCR. Crossspecies PCR and sequencing was used to identify gerbil transcripts for IFNγ, IL-12p40, IL-10 and TGFβ. The ratio of cytokines to β-actin was determined by computer image analysis. Results: Gastric IFNγ transcripts in H pylori infected gerbils were significantly increased at 12 (p<0.05) and 36 weeks (p<0.01) p.i. compared to uninfected controls. (IFNγ:β-actin ratio 12 weeks 0.85 v 0.057; 36 weeks 1.51 v 0.16). IL-12p40 transcripts in H pylori infected gerbils were significantly increased (p<0.05) at 36 weeks p.i. compared to controls (1.512 v 0.512). In contrast, no differences in IL-10 or TGFβ transcripts were observed with H pylori infection, although an age-related increase in TGFβ transcripts was evident in both infected and control gerbils. Conclusions: Long term chronic infection with H pylori in the Mongolian gerbil is associated with upregulation of the Th1 cytokines IFN-γ and IL-12p40 n the gastric mucosa. The lack of upregulation of key immunomodulatory cytokines IL-10 and TGF-β in H pylori infection may contribute to the severe pathology associated with infection in the Mongolian gerbil.
ACCESSION #
9747628

 

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