Untersuchungen zur Expression potentiell allergierelevanter Gene

Asthma bronchiale ist eine chronische Atemwegsentzündung. Der Körper reagiert auf ein harmloses Antigen mit einer Überreaktion des Immunsy- stems was zu einer Atemwegshyperreagibilität und einer chronischen Ent- zündung in den Atemwegen führt. Diese Immunantwort ist Th2-dominiert und die Zytokine de...

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Bibliographic Details
Main Author: Heppenheimer, Charlotte
Contributors: Garn, Holger (Priv. Doz. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2014
Online Access:PDF Full Text
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Bronchial asthma is a chronical inflammation of the airways. The bodys immune system shows an overreaction to harmless antigens, leading to an hyperreactivity and a chronical inflammation of the airways. This immune response ist dominated by Th2-Cells and its cytokins, both playing an important role in the pathogenesis of asthma. Corticosteroids calming inflammation and ß2-mimetics dilatating the airways are, to this point, the main components of asthma therapy. This treatment ist mostly symptomatic and does not suffice to treat all forms of asthma. Also there are a lot of side effects due to the wide effectiveness of corticosteroids. New strategies in therapy focus on the central role of Th2 cells in the pathogenesis of asthma, so far without great success. In order to find a better cure for asthma we studied the expression of so far unknown genes whose expression was found to be higher in the pulmonal t-lymphocytes of mice with chronical asthma than of those with acute asthma. In a first step was prove, by quantitatve PCR, that there is an increase in the expression of genes 1,2,3 and 5 from the pulmonary t-lymphocytes of healthy mice, to mice with acute asthma, to mice with chronical asthma. So these genes might play an important role in the chronification and pathogenesis of asthma. To minimize side effects, the expression of genes, who are to be therapeutically influenced, should be organ- or cellspecific. In a second step we tested the expression of the genes in the organs of healthy mice via qualitative PCR. A very high expression was found in lymph nodes, leading to the conclusion that there is a high expression of the genes in differentiated t-lymphocytes. All other organs also expressed the genes, but weaker. While some of these organs have lymphatic tissue in them and therefor contain differentiated t-lymphocytes (f.e. bowel), there is no explanation for the basic expression of the genes in other organs (f.e. testicles). In a third step we tested the expression of the genes via quantitative PCR in murine cells. Outstanding was the high expression of genes 1-5 in epithelial cells LA-4. This expression could explain the expression of the genes in epithelial organs (f.e. testicles). EL-4 cells as t-lymphocytes didnt show, as expected, the highest expression of the genes. This could lead to the conlusion that only differentiated t-cells show a high expression of the tested genes. The further study of genes 1,2,3 and 5 is of scientific interest, as we found an increase of their expression in t-lymphocytes of mice with chronical asthma. For gene 4 this increase could not be found. If these genes might be useful as a therapeutical target is in question, because of their ubiquitary expression. It would be interesting to take a closer look at the studied genes and their function, and to find out if the chronification of asthma could be averted by selectively blocking the expression of these genes.