Cyclooxygenase-2-deficient mice are resistant to endotoxin-induced inflammation and death.
FASEB J
; 17(10): 1325-7, 2003 Jul.
Article
en En
| MEDLINE
| ID: mdl-12738799
ABSTRACT
Sepsis is a systemic inflammatory response to a blood-borne infection that is associated with an extremely high rate of morbidity and mortality. The present study investigates the role of cyclooxygenase (COX)-2 in host responses to bacterial endotoxemia. After administration of Escherichia coli lipopolysaccharide, 50% of wild-type mice die within 96 h. COX-2 deficient mice displayed a dramatic improvement in survival with reduced leukocyte infiltration into critical organs (kidneys and lungs) and a blunted and delayed induction of the cytokine inducible genes nitric oxide synthase 2 and heme oxygenase-1. Translocation and activation of transcription factors important for signaling events during an inflammatory response, such as nuclear factor (NF)-kappaB, were also markedly reduced. While the absence of COX-2 did not alter the induction of several pro-inflammatory cytokines in tissue macrophages, induction of the anti-inflammatory cytokine IL-10 was exaggerated. Administration of IL-10 to wild-type mice reduced NF-kappaB activation. Taken together, our data suggest that COX-2 deficient mice are resistant to many of the detrimental consequences of endotoxemia. These beneficial effects occur, in part, by a compensatory increase in IL-10 that counterbalances the pro-inflammatory host response to endotoxemia.
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Base de datos:
MEDLINE
Asunto principal:
Prostaglandina-Endoperóxido Sintasas
/
Endotoxemia
/
Isoenzimas
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos