A phosphatidyl-inositol-3-kinase-dependent anti-inflammatory pathway activated by Salmonella in epithelial cells.
Salmonella activates the phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway in epithelial cells, but its role in inflammation has not been previously elucidated. We show here that inhibition of PI3K in T84 intestinal epithelial cells results in augmentation of Salmonella-induced interleukin-8 (IL-8) production at the level of both protein and mRNA. The mechanism of this effect appears to involve altered activation of the extracellular growth factor-regulated kinase (ERK), a molecule that is implicated in the regulation of IL-8 expression. These results identify activation of the PI3K/Akt pathway as an anti-inflammatory signal that may contribute to the establishment of Salmonella in the intestine.
Huang
Fu-Chen
FC
Department of Pediatrics, Pediatric Gastroenterology and Nutrition Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Li
Qian
Q
Cherayil
Bobby J
BJ
D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000382:microbiology*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015398:Signal Transduction
D016209:Interleukin-8; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human