R ecognition of apoptotic cells (AC)3 elicits immunological consequences that have received considerable attention during recent years. Professional phagocytes such as dendritic cells and macrophages recognize AC via so called "eat me" signals, with concomitant phagocytosis (1). The uptake of AC avoids secondary necrosis and thus the release of harmful cell contents. Moreover, ingestion of apoptotic material actively provokes a macrophage phenotype shift, which helps to terminate perpetuating inflammatory responses. The altered macrophage phenotype is characterized by the release of antiinflammatory mediators such as TGF- or prostaglandin E 2 (2). Additionally, these polarized macrophages suppress the production of reactive oxygen species (3), NO (4), and proinflammatory cytokines such as TNF-␣, IL-1, and IL-6 (1). AC block NF-B activation, which contributes to the diminished production of proinflammatory cytokines, although mechanisms of how NF-B is inhibited remain unclear (5). Cvetanovic and Ucker demonstrated that an attenuated NF-B transactivation response and an AC-elicited reduction in target gene expression are cell-cell contact-dependent but phosphatidylserine-independent (6). Furthermore, it was noticed that NF-B binding to DNA as well as IB degradation were not affected by AC. As an alternative explanation, it was proposed that a limited amount of p300, an established co-factor of NF-B-dependent proinflammatory gene expression (7), decreases its activity, although underlying mechanisms remain obscure (5). A potential candidate known to interact with p300 and thereby attenuating an inflammatory response is peroxisome proliferatoractivated receptor ␥ (PPAR␥) (8).PPAR␥ belongs to the nuclear hormone receptor superfamily of ligand-activated transcription factors and originally has been characterized to be important for adipogenesis and glucose metabolism (9). Induction of PPAR␥ target genes requires ligand binding, heterodimerization with the retinoid X receptor (RXR), and subsequent binding to specific peroxisome proliferator response elements. Besides transcriptional activation, PPAR␥ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.1 This work was supported by grants from Deutsche Forschungsgemeinschaft (Br 999, FOG 784, Excellence Cluster Cardiopulmonary System), Deutsche Krebshilfe, Sander Foundation, LiFF, and European Community (PROLIGEN).2 Address correspondence and reprint requests to Dr. Bernhard Brüne, Goethe-University Frankfurt am Main, Faculty of Medicine, Institute of Biochemistry I/Zentrum für Arzneimittelforschung, -Entwicklung und -Sicherheit (ZAFES), Pathobiochemistry, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail address: bruene@ zbc.kgu.de 3 Abbreviations used in this paper: AC, apoptotic cells; ChIP, chromatin immunoprecipitation; d/n, dominant negative; HDAC, histone deacetylase; iNOS, inducible NO s...
