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T-cell cytokines associated with inflammatory bowel disease in MDR knockout and chimera models.

T-CELL CYTOKINES ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE IN MDR KNOCKOUT AND CHIMERA MODELS. Dale S. carter, Julia M. Schmitz, Vance J. McCracken, Reed A Dimmitt, Robin G. Lorenz, and Jennifer T. Thomas, Belmont University, Nashville, Tennessee (DSC, JTT), and University of Alabama--Birmingham, Birmingham, Alabama; (JMS, VJM, RAD, RGL). Chemotherapy resistance, Alabama (J,MS, VJM, RAD, RGL). Chemotherapy, Birmingham, Alabama (JMS, VJM, RAD, RGL). Chemotherapy resistance has become one of the most serous difficulties resistance has become one of the most serious difficulties associated with cancer treatment. The multidrug resistant (MDR)gene, which encodes for p-glycoprotein, has been shown to contribute to this chemotherapy resistance by pumping lethal doses of chemother-apeutic agents out of concer cells. In order to determine the normal function of p-glycoprotein, a knockout mouse was created. Interestingly, the loss of p-glycoprotein in the knockout mouse resulted in serious Inflammatory Bowel Disease (IBD) IBD is thought to be due to a dysregulated immune response to the toxis produced by the microbiota of the gastrointestinal tract; Past studies have ruled out CD8(+) T cells as the cause of IBD and it is theorized that another subset of T cells, CD4(+) T cells, is responsible for this disease. In order to determine what particular CD4+ T cell types are causing IBD, I extracted RNA from colon samples of wild type, mdr knockout, and two bone marrow chimeras that express p-glycoprotein in either bone marrow derived or intestinal epithelial cells. The RNA was transcribed into cDNA and then put through Real-Time reverse transcriptase PCR to detect the specific cytokines derived from the different T cell types. The cytokines of Thl, Treg, and Th17 cells were detected in the highest amounts of Thl, Treg, and Th17 cells were detected in the highest amounts. Cytokines from Th2 cells showed the lowest level of expression. In all the diseased animal models the Th17 cytokines were detected in vastly higher amounts. This seems to indicate that the Th17 cell may play a more important role in causing IBD.
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Title Annotation:MIDDLE REGION; multidrug resistance
Publication:Journal of the Tennessee Academy of Science
Article Type:Report
Geographic Code:1USA
Date:Jul 1, 2008
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