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The efficacy of these agents in reducing inflammation suggests a dominant proinflammatory role for the COX pathway. However, the actions of COX metabolites are complex, and certain prostanoids, such as PGE2, in some circumstances actually inhibit immune and inflammatory responses. In these studies, we examine the hypothesis that anti-inflammatory actions of NSAIDs may be due, in part, to inhibition of thromboxane A2 synthesis. To study the immunoregulatory actions of thromboxane A2, we used mice with a targeted disruption of the gene encoding the thromboxane-prostanoid (TP) receptor. Both mitogen-induced responses and cellular responses to alloantigen were substantially reduced in TP\u2212\/\u2212 spleen cells. Similar attenuation was observed with pharmacological inhibition of TP signaling in wild-type splenocytes, suggesting that reduced responsiveness was not due to subtle developmental abnormalities in the TP-deficient mice. The absence of TP receptors reduced immune-mediated tissue injury following cardiac transplant rejection, an in vivo model of intense inflammation. Taken together, these findings show that thromboxane augments cellular immune responses and inflammatory tissue injury. Specific inhibition of the TP receptor may provide a more precise approach to limit inflammation without some of the untoward effects associated with NSAIDs.<\/jats:p>","DOI":"10.4049\/jimmunol.171.12.6389","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:30:32Z","timestamp":1398029432000},"page":"6389-6395","source":"Crossref","is-referenced-by-count":63,"title":["Proinflammatory Actions of Thromboxane Receptors to Enhance Cellular Immune Responses"],"prefix":"10.1093","volume":"171","author":[{"given":"Dennis W","family":"Thomas","sequence":"first","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo N","family":"Rocha","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Nataraj","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F","family":"Spurney","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly H","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina , Chapel Hill, NC 27514"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"Coffman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,12,15]]},"reference":[{"key":"2026020210244378900_R1","first-page":"1193","volume-title":"Physiol. 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