Premium
Peroxisome proliferator‐activated receptor γ contributes to T lymphocyte apoptosis during sepsis
Author(s) -
Soller Mathias,
Tautenhahn Anja,
Brüne Bernhard,
Zacharowski Kai,
John Stefan,
Link Hartmut,
Knethen Andreas
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0205058
Subject(s) - sepsis , peroxisome proliferator activated receptor , biology , apoptosis , agonist , ppar agonist , immunology , receptor , cancer research , microbiology and biotechnology , biochemistry
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.