Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Observations Sur Quelques Foug\ue8res Des D\ue9pots Houillers D\u27Asie Mineure

Volume: 44Start Page: 195End Page: 21

Sur La D\ue9couverte, Par M. Amalitzky, De Glossopteris Dans Le Permien Sup\ue9rieur De Russie

Volume: 45Start Page: 392End Page: 39

NACA Technical Notes

From Summary: "A method for the experimental determination of the rate of infiltration of air into aircraft cabins during flight has been developed and tested. This method consists of releasing a quantity of gas in the cabin and calculating the infiltration rate from the measured rate of change of the gas concentration. The results of the flight tests indicate that after the infiltration rate is established at one altitude and airspeed, the infiltration rates at other altitudes and airspeeds can be calculated.

Flore fossile des g\ueetes de charbon du Tonkin,

Atlas (1902