Salmonella typhimurium infection in the porcine intestine: evidence for caspase-3-dependent and -independent programmed cell death.
The normal intestinal epithelium is renewed with a turnover rate of 3-5 days. During Salmonella infection increased cell loss is observed, possibly as a result of programmed cell death (PCD). We have, therefore, studied the effects of Salmonella Typhimurium infection on three elements involved in PCD: caspase-3 activation, c-Jun phosphorylation on serine 63 (both detected by immunocytochemistry), and DNA fragmentation (detected by TUNEL reaction), using a pig jejunal loop model. Additionally, we used nuclear staining for detecting signs of classical apoptosis. Activated caspase-3 was detected in scattered epithelial cells and the number of positive cells increased with increasing times of exposure to Salmonella (P<0.0001). An increase in phospho-c-Jun in epithelial cells was already detectable 5 min after infection and often occurred in cells that appeared not to be invaded by the organism. Changes in caspase-3 activation and c-Jun phosphorylation were most marked in the proximal region of the jejunum. Although rarely observed in the epithelium, proper TUNEL-positive cells were frequently found in the intestinal lumen. Some, but not all, TUNEL-positive cells were also positive for caspase-3, indicating that both caspase-3-dependent and -independent pathways of PCD increased upon infection.
Schauser
Kirsten
K
Department of Basic Animal and Veterinary Sciences, The Royal Veterinary and Agricultural University, Gronnegaardsvej 7, 1870 Frederiksberg C, Denmark. ks@kvl.dk
Olsen
John Elmerdahl
JE
Larsson
Lars-Inge
LI
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007583:Jejunum / Q000382:microbiology* / Q000473:pathology; D012480:Salmonella Infections / Q000473:pathology*; D012486:Salmonella typhimurium; D034421:Sus scrofa
D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D020169:Caspases