Prostaglandin E2 receptors EP2 and EP4 are down-regulated in human mononuclear cells after injury.

Strong, V E; Winter, J; Yan, Z; Smyth, G P; Mestre, J R; Maddali, S; Schaefer, P A; Yurt, R W; Stapleton, P P; Daly, J M

Strong, V E; Winter, J; Yan, Z; Smyth, G P; Mestre, J R; Maddali, S; Schaefer, P A; Yurt, R W; Stapleton, P P; Daly, J M.

Afiliación

Strong VE; Department of Surgery, New York Presbyterian Hospital-Weill Medical College of Cornell Univerity, New York, NY 10021, USA.

Surgery ; 130(2): 249-55, 2001 Aug.

Article en En | MEDLINE | ID: mdl-11490357

RESUMEN

BACKGROUND: Recent characterization of prostaglandin receptor subtypes shows that each is critical to cellular functions and operates through separate signaling pathways that may explain differing effects of prostanoids. This study aimed to determine whether prostaglandin receptors EP2 and EP4 are modulated after injury and to evaluate the effect of prostaglandin E(2) (PGE(2)) addition and blockade on EP receptor expression. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from 10 patients sustaining fracture or burn injury and 10 control subjects were stimulated with lipopolysaccharide +/- NS-398, an inhibitor of PGE(2) production. Samples were evaluated for production of PGE(2), tumor necrosis factor--alpha, and leukotriene B(4) as well as mRNA expression of EP receptors and COX-2. EP receptor expression was also evaluated after treating control PBMCs with PGE(2). RESULTS: PBMCs from injured patients exhibited significant increases in PGE(2) production and COX-2 mRNA compared with control subjects, and these increases were inhibited by NS-398. In contrast, EP2 and EP4 receptors were markedly down-regulated after injury and NS-398 restored expression to control levels. Decreased EP2 and EP4 receptor expression after injury was replicated by coincubation of PBMCs with PGE(2). CONCLUSIONS: Specific PGE(2) receptors are down-regulated after injury and NS-398 reverses this response. Furthermore, PGE(2) mediates EP2 and EP4 down-regulation. These data suggest that specific EP receptor subtypes may provide critical targets for augmenting the immune response after injury in humans.

Asunto(s)

Quemaduras/inmunología; Fracturas Óseas/inmunología; Leucocitos Mononucleares/inmunología; Receptores de Prostaglandina E/genética; Adulto; Anciano; Quemaduras/metabolismo; Ciclooxigenasa 2; Inhibidores de la Ciclooxigenasa 2; Inhibidores de la Ciclooxigenasa/farmacología; Dinoprostona/análisis; Dinoprostona/biosíntesis; Regulación hacia Abajo/efectos de los fármacos; Regulación hacia Abajo/inmunología; Femenino; Fracturas Óseas/metabolismo; Expresión Génica/efectos de los fármacos; Expresión Génica/inmunología; Humanos; Técnicas In Vitro; Isoenzimas/genética; Leucocitos Mononucleares/metabolismo; Leucotrieno B4/análisis; Leucotrieno B4/biosíntesis; Receptores de Lipopolisacáridos/genética; Lipopolisacáridos/farmacología; Masculino; Proteínas de la Membrana; Persona de Mediana Edad; Nitrobencenos/farmacología; Prostaglandina-Endoperóxido Sintasas/genética; ARN Mensajero/análisis; Receptores de Prostaglandina E/inmunología; Receptores de Prostaglandina E/metabolismo; Subtipo EP2 de Receptores de Prostaglandina E; Subtipo EP4 de Receptores de Prostaglandina E; Transducción de Señal/inmunología; Sulfonamidas/farmacología; Factor de Necrosis Tumoral alfa/análisis; Factor de Necrosis Tumoral alfa/biosíntesis

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quemaduras / Leucocitos Mononucleares / Receptores de Prostaglandina E / Fracturas Óseas Idioma: En Revista: Surgery Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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