Gene interactions and pathways from curated databases and text-mining
Am J Physiol Cell Physiol 2002, PMID: 12055072

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

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.

Document information provided by NCBI PubMed

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

No curated data.