Peroxisome proliferator-activated receptor γ contributes to T lymphocyte apoptosis during sepsis

Journal of Leukocyte Biology

Stefan John²  Bernhard Brüne⁴  Anja Tautenhahn⁴  Kai Zacharowski³  Mathias Soller⁴  Andreas von Knethen⁴  Hartmut Link¹ 

[1] Westpfalz-Klinikum Kaiserslautern, Department of Internal Medicine I, Germany Westpfalz-Klinikum Kaiserslautern, Department of Internal Medicine I, Germany Westpfalz-Klinikum Kaiserslautern, Department of Internal Medicine I, Germany;Department of Medicine IV-Experimental Division, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany; and Department of Medicine IV-Experimental Division, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany; and Department of Medicine IV-Experimental Division, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany; andDepartment of Anesthesiology, Molecular Cardioprotection and Inflammation Group, Faculty of Medicine, University of Düsseldorf, Germany; Department of Anesthesiology, Molecular Cardioprotection and Inflammation Group, Faculty of Medicine, University of Düsseldorf, Germany; Department of Anesthesiology, Molecular Cardioprotection and Inflammation Group, Faculty of Medicine, University of Düsseldorf, Germany;Department of Biochemistry I, University Hospital, Johann Wolfgang Goethe-University Frankfurt, Germany; Department of Biochemistry I, University Hospital, Johann Wolfgang Goethe-University Frankfurt, Germany; Department of Biochemistry I, University Hospital, Johann Wolfgang Goethe-University Frankfurt, Germany;

关键词: cell death;    bacterial;    inflammation;    leukopenia;   

DOI  :  10.1189/jlb.0205058

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

In the last two decades, extensive research failed to significantly improve the outcome of patients with sepsis. In part, this drawback is based on a gap in our knowledge about molecular mechanisms understanding the pathogenesis of sepsis. During sepsis, T cells are usually depleted. Recent studies in mice and human cells suggested a role of the peroxisome proliferator-activated receptor γ (PPARγ) in provoking apoptosis in activated T lymphocytes. Therefore, we studied whether expression/activation of PPARγ might contribute to T cell death during sepsis. We observed PPARγ up-regulation in T cells of septic patients. In contrast to controls, PPARγ expressing cells from septic patients responded with apoptosis when exposed to PPARγ agonists. Cell demise was attenuated by SR-202, a synthetic PPARγ antagonist, and specificity was further verified by excluding a proapoptotic response to a PPARα agonist. We propose that up-regulation of PPARγ sensitizes T cells of septic patients to undergo apoptosis. PPARγ activation in T cells requires an exogenous PPARγ agonist, which we identified in sera of septic patients. Septic sera were used to study reporter gene expression containing a PPAR-responsive element. We conclude that PPARγ plays a significant role in T cell apoptosis, contributing to lymphocyte loss in sepsis. Thus, inhibition of PPARγ may turn out to be beneficial for patients suffering from lymphopenia during sepsis.

【 授权许可】

Unknown