Am J Physiol Cell Physiol 2002,
PMID: 12055072
Kilpatrick, Laurie E; Lee, Julia Y; Haines, Kathleen M; Campbell, Donald E; Sullivan, Kathleen E; Korchak, Helen M
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.
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Text Mining Data
p60TNFR → TNF-alpha: "
In adherent neutrophils,
TNF-alpha triggers association of both protein kinase C (PKC)-delta and phosphatidylinositol (PI) 3-kinase with the
p60TNFR
"
phosphatidylinositol (PI) 3-kinase → TNF-alpha: "
In adherent neutrophils, TNF-alpha triggers association of both protein kinase C (PKC)-delta and phosphatidylinositol (PI) 3-kinase with the p60TNFR
"
protein kinase C (PKC)-delta → TNF-alpha: "
In adherent neutrophils, TNF-alpha triggers association of both protein kinase C (PKC)-delta and phosphatidylinositol (PI) 3-kinase with the p60TNFR
"
NFkappaB → TNF-alpha: "
Inhibition of either PKC-delta or PI 3-kinase attenuated TNF-alpha mediated activation of the antiapoptotic transcription factor NFkappaB
"
NFkappaB → PI 3-kinase: "
Inhibition of either PKC-delta or PI 3-kinase attenuated TNF-alpha mediated activation of the antiapoptotic transcription factor NFkappaB
"
Manually curated Databases
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