{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:09:18Z","timestamp":1789409358997,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The peroxisome proliferator-activated receptor \u03b3 (PPAR-\u03b3) belongs to a receptor superfamily of ligand-activated transcription factors involved in the regulation of metabolism and inflammation. Oral administration of PPAR-\u03b3 agonists ameliorates the clinical course and histopathological features in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS), and PPAR-\u03b3 agonist treatment of PBMCs from MS patients suppresses PHA-induced cell proliferation and cytokine secretion. These effects are pronounced when cells are preincubated with the PPAR-\u03b3 agonists and reexposed at the time of stimulation, indicating a sensitizing effect. To characterize the mechanisms underlying this sensitizing effect, we analyzed PPAR-\u03b3 expression in PMBCs of MS patients and healthy controls. Surprisingly, MS patients exhibited decreased PPAR-\u03b3 levels compared with controls. PHA stimulation of PBMCs from healthy controls resulted in a significant loss of PPAR-\u03b3, which was prevented by in vitro preincubation of the cells or in vivo by long-term oral medication with the PPAR-\u03b3 agonist pioglitazone. Differences in PPAR-\u03b3 expression were accompanied by changes in PPAR-\u03b3 DNA-binding activity, as preincubation with pioglitazone increased DNA binding of PPAR-\u03b3. Additionally, preincubation decreased NF-\u03baB DNA-binding activity to control levels, whereas the inhibitory protein I\u03baB\u03b1 was increased. In MS patients, pioglitazone-induced increase in PPAR-\u03b3 DNA-binding activity and decrease in NF-\u03baB DNA-binding activity was only observed in the absence of an acute MS relapse. These results suggest that the sensitizing effect observed in the preincubation experiments is mediated by prevention of inflammation-induced suppression of PPAR-\u03b3 expression with consecutive increase in PPAR-\u03b3 DNA-binding activity.<\/jats:p>","DOI":"10.4049\/jimmunol.175.8.4948","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:28:35Z","timestamp":1398032915000},"page":"4948-4955","source":"Crossref","is-referenced-by-count":89,"title":["Proinflammatory Stimulation and Pioglitazone Treatment Regulate Peroxisome Proliferator-Activated Receptor \u03b3 Levels in Peripheral Blood Mononuclear Cells from Healthy Controls and Multiple Sclerosis Patients"],"prefix":"10.1093","volume":"175","author":[{"given":"Luisa","family":"Klotz","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Giese","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Sastre","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Percy","family":"Knolle","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Experimental Immunology, University of Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klockgether","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T","family":"Heneka","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Mu\u0308nster , Munster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,10,15]]},"reference":[{"key":"2026020212155234800_R1","first-page":"291","volume-title":"Nat. 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