Decreased gastric bacterial killing and up-regulation of protective genes in small intestine in gastrin-deficient mouse.
Gastrin regulates gastric acid secretion, believed to be primarily responsible for killing ingested microbes. We examined gastric killing of gavaged E. coli in gastrin-deficient mice, which have decreased gastric acid production. Additionally, the expression of intestinal genes involved in epithelial protection were analyzed: the mucus layer glycoprotein muclin, the polymeric Ig receptor, trefoil factor 3, and small proline-rich protein 2a (sprr2a). Gastric pH was 2.5 pH units greater in gastrin-deficient mice, and E. coli survival was increased greater than 20-fold at 10 min after gavage compared to control. Muclin and sprr2a gene expression were significantly increased (2.0- and 2.6-fold) in the intestine, and antibiotic treatment reversed these effects. In conclusion, reduced gastric acid secretion results in increased survival of ingested microorganisms in gastrin-deficient mice. Bacterial survival is associated with increased expression of muclin and sprr2a in the intestine, indicating that these genes play protective roles in the intestine.
Sun
Francis J
FJ
Laboratory Animal Resources, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Kaur
Simran
S
Ziemer
Donna
D
Banerjee
Snigdha
S
Samuelson
Linda C
LC
De Lisle
Robert C
RC
D000818:Animals; D001483:Base Sequence; D055233:Cornified Envelope Proline-Rich Proteins; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005755:Gastrins / Q000172:deficiency*; D006133:Growth Substances / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011498:Protein Precursors / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D015854:Up-Regulation
D055233:Cornified Envelope Proline-Rich Proteins; D004269:DNA, Bacterial; D005755:Gastrins; D006133:Growth Substances; D008565:Membrane Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; C491091:Sprr2a1 protein, mouse; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3