Genetic pathogenesis of tissue injury-induced apoptosis of immunocompetent and parenchymal cells

• Antragsteller: Professor Dr. Wolfgang Ertel, seit 12/2006
• Fachliche Zuordnung: Orthopädie, Unfallchirurgie, rekonstruktive Chirurgie
• Förderung: Förderung von 2003 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5408575

Severe tissue trauma leads to an early activation of the innate immune system with systemic inflammation followed by its downregulation and consequent immunosuppression. Both cause organ damage and finally multiple organ failure. Systemic inflammation as well as immunosuppression is characterized through a dysregulation of cell homeostasis which is predominantly regulated through apoptosis. Although some mechanisms of those tissue trauma induced immunological disorders have been described on a cellular level, the downstream gene based mechanisms of altered apoptosis need to be investigated. Using a mouse model of systemic tissue injury (hemorrhage) with or without local tissue trauma (laparotomy) it is the principal objective to explore time-dependent gene expression of apoptosis inducing proteins in correlation with functional disorders of immunocompetent and parenchymal cells. Moreover, using gene modulation with adenovirus and transfection of specific cells with vectors for anti-apoptotic proteins as well as using knock-out mice the importance of apoptosis inducing proteins will be confirmed. In addition, using microarray analyses unknown genes which may play a pivotal role for tissue damage induced apoptosis will be screened. Finally, gene expression of apoptosis regulating proteins will be determined in immunocompetent cells from trauma victims followed by gene modulation using adenovirus transfection.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1151: Immun- und Stoffwechselmodulation durch schweres Gewebstrauma
• Ehemaliger Antragsteller: Privatdozent Dr. Andreas Oberholzer, bis 12/2006
• Beteiligte Person: Dr. Sven Kevin Tschöke