This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Soller, M. Articles by von Knethen, A. Search for Related Content PubMed PubMed Citation Articles by Soller, M. Articles by von Knethen, A.

(Journal of Leukocyte Biology. 2006;79:235-243.)
© 2006 by Society for Leukocyte Biology

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

Mathias Soller^*, Anja Tautenhahn^*, Bernhard Brüne^*, Kai Zacharowski, Stefan John, Hartmut Link and Andreas von Knethen^*,1

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

¹ Correspondence: Department of Biochemistry I, University Hospital, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail: v_knethen{at}zbc.kgu.de

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 (PPAR) in provoking apoptosis in activated T lymphocytes. Therefore, we studied whether expression/activation of PPAR might contribute to T cell death during sepsis. We observed PPAR up-regulation in T cells of septic patients. In contrast to controls, PPAR expressing cells from septic patients responded with apoptosis when exposed to PPAR agonists. Cell demise was attenuated by SR-202, a synthetic PPAR antagonist, and specificity was further verified by excluding a proapoptotic response to a PPAR agonist. We propose that up-regulation of PPAR sensitizes T cells of septic patients to undergo apoptosis. PPAR activation in T cells requires an exogenous PPAR 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 PPAR plays a significant role in T cell apoptosis, contributing to lymphocyte loss in sepsis. Thus, inhibition of PPAR may turn out to be beneficial for patients suffering from lymphopenia during sepsis.

Key Words: cell death • bacterial • inflammation • leukopenia

This article has been cited by other articles:

				R. C. Reddy, V. R. Narala, V. G. Keshamouni, J. E. Milam, M. W. Newstead, and T. J. Standiford Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-{gamma} Blood, November 15, 2008; 112(10): 4250 - 4258. [Abstract] [Full Text] [PDF]

				M. Soller, S. Drose, U. Brandt, B. Brune, and A. von Knethen Mechanism of Thiazolidinedione-Dependent Cell Death in Jurkat T Cells Mol. Pharmacol., June 1, 2007; 71(6): 1535 - 1544. [Abstract] [Full Text] [PDF]

				S.-H. Jo, C. Yang, Q. Miao, M. Marzec, M. A. Wasik, P. Lu, and Y. L. Wang Peroxisome Proliferator-Activated Receptor {gamma} Promotes Lymphocyte Survival through Its Actions on Cellular Metabolic Activities J. Immunol., September 15, 2006; 177(6): 3737 - 3745. [Abstract] [Full Text] [PDF]