{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:37:59Z","timestamp":1791315479654,"version":"4.3.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bacterial endotoxin (LPS)-mediated sepsis involves severe, dysregulated inflammation that injures the lungs and other organs, often fatally. Vascular endothelial cells are both key mediators and targets of LPS-induced inflammatory responses. The nuclear hormone receptor peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) exerts anti-inflammatory actions in various cells, but it is unknown whether it modulates inflammation through actions within endothelial cells. To determine whether PPAR\u03b3 acts within endothelial cells to diminish endotoxemic lung inflammation and injury, we measured inflammatory responses and mediators in mice with endothelial-targeted deletion of PPAR\u03b3. Endothelial cell PPAR\u03b3 (ePPAR\u03b3) knockout exacerbated LPS-induced pulmonary inflammation and injury as shown by several measures, including infiltration of inflammatory cells, edema, and production of reactive oxygen species and proinflammatory cytokines, along with upregulation of the LPS receptor TLR4 in lung tissue and increased activation of its downstream signaling pathways. In isolated LPS-stimulated endothelial cells in vitro, absence of PPAR\u03b3 enhanced the production of numerous inflammatory markers. We hypothesized that the observed in vivo activity of the ligand-activated ePPAR\u03b3 may arise, in part, from nitrated fatty acids (NFAs), a novel class of endogenous PPAR\u03b3 ligands. Supporting this idea, we found that treating isolated endothelial cells with physiologically relevant concentrations of the endogenous NFA 10-nitro-oleate reduced LPS-induced expression of a wide range of inflammatory markers in the presence of PPAR\u03b3, but not in its absence, and also inhibited neutrophil mobility in a PPAR\u03b3-dependent manner. Our results demonstrate a key protective role of ePPAR\u03b3 against endotoxemic injury and a potential ePPAR\u03b3-mediated anti-inflammatory role for NFAs.<\/jats:p>","DOI":"10.4049\/jimmunol.1201487","type":"journal-article","created":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T05:55:16Z","timestamp":1351317316000},"page":"5411-5420","source":"Crossref","is-referenced-by-count":54,"title":["Endothelial Cell Peroxisome Proliferator\u2013Activated Receptor \u03b3 Reduces Endotoxemic Pulmonary Inflammation and Injury"],"prefix":"10.1093","volume":"189","author":[{"given":"Aravind T","family":"Reddy","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya P","family":"Lakshmi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Kleinhenz","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy L","family":"Sutliff","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Michael","family":"Hart","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju C","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,1]]},"reference":[{"key":"2025032409370836000_r1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The pathophysiology and treatment of sepsis","volume":"348","author":"Hotchkiss","year":"2003","journal-title":"N. 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