Your browser doesn't support javascript.
loading
A role for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic signaling in the human neutrophil.
Kilpatrick, Laurie E; Lee, Julia Y; Haines, Kathleen M; Campbell, Donald E; Sullivan, Kathleen E; Korchak, Helen M.
Afiliación
  • Kilpatrick LE; Department of Pediatrics, University of Pennsylvania School of Medicine and the Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. kilpatrick@emailchop.edu
Am J Physiol Cell Physiol ; 283(1): C48-57, 2002 Jul.
Article en En | MEDLINE | ID: mdl-12055072
The proinflammatory cytokine tumor necrosis factor (TNF)-alpha has been implicated in the attenuation of neutrophil spontaneous apoptosis during sepsis. Antiapoptotic signaling is principally mediated through the p60TNF receptor (p60TNFR). In neutrophils, TNF-alpha is an incomplete secretagogue and requires input from a ligated integrin(s) for neutrophil activation. In adherent neutrophils, TNF-alpha triggers association of both protein kinase C (PKC)-delta and phosphatidylinositol (PI) 3-kinase with the p60TNFR. In this study, a role for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic signaling was examined. TNF-alpha inhibited spontaneous apoptosis in fibronectin-adherent neutrophils, and this antiapoptotic signaling was blocked by the PKC-delta inhibitor rottlerin, but not by an inhibitor of Ca(2+)-dependent PKC isotypes, Go-6976. Inhibition of PI 3-kinase by LY-294002 also inhibited TNF-alpha-mediated antiapoptotic signaling. Cycloheximide blocked TNF-alpha-mediated antiapoptotic signaling, suggesting protein synthesis is required. Inhibition of either PKC-delta or PI 3-kinase attenuated TNF-alpha-mediated activation of the antiapoptotic transcription factor NFkappaB. Thus both PKC-delta and PI 3-kinase have essential roles in TNF-alpha-mediated antiapoptotic signaling in adherent neutrophils.
Asunto(s)
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Quinasa C / Transducción de Señal / Factor de Necrosis Tumoral alfa / Apoptosis / Fosfatidilinositol 3-Quinasas / Isoenzimas / Neutrófilos Límite: Adult / Humans Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Quinasa C / Transducción de Señal / Factor de Necrosis Tumoral alfa / Apoptosis / Fosfatidilinositol 3-Quinasas / Isoenzimas / Neutrófilos Límite: Adult / Humans Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos