Gene interactions and pathways from curated databases and text-mining
FASEB J 2006, PMID: 16720733

Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity.

Dang, Pham My-Chan; Elbim, Carole; Marie, Jean-Claude; Chiandotto, Mélanie; Gougerot-Pocidalo, Marie-Anne; El-Benna, Jamel

Interleukin-10 (IL-10) exerts its anti-inflammatory properties by down-regulating polymorphonuclear neutrophil (PMN) functions such as reactive oxygen species (ROS) production via NADPH oxidase. The molecular mechanisms underlying this process are unclear. Partial phosphorylation of the NADPH oxidase cytosolic component p47(PHOX) induced by proinflammatory cytokines, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha, is essential for priming ROS production by PMN. The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNFalpha-induced p47(PHOX) phosphorylation and to investigate the molecular mechanisms involved in this effect. We found that IL-10 selectively inhibited GM-CSF- but not TNFalpha-induced p47PHOX phosphorylation in a concentration-dependent manner. As GM-CSF-induced p47PHOX phosphorylation is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), we tested the effect of IL-10 on this pathway. We found that IL-10 inhibited GM-CSF-induced ERK1/2 activity in an immunocomplex kinase assay. This inhibitory effect was confirmed by analyzing the phosphorylation status of the endogenous substrate of ERK1/2, p90RSK, in intact PMN. Furthermore, IL-10 decreased ROS production by adherent GM-CSF-treated PMN in keeping with the higher ROS production observed in whole blood from IL-10 knockout mice compared to their wild-type counterparts. Together, these results suggest that IL-10 inhibits GM-CSF-induced priming of ROS production by inhibiting p47PHOX phosphorylation through a decrease in ERK1/2 activity. This IL-10 effect could contribute to the tight regulation of NADPH oxidase activity at the inflammatory site.

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Text Mining Data

p47PHOX → GM-CSF: " Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF induced p47PHOX phosphorylation through a decrease in ERK1/2 activity "

p47PHOX — interleukin-10: " Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF induced p47PHOX phosphorylation through a decrease in ERK1/2 activity "

p47 ⊣ IL-10: " The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNFalpha induced p47 ( PHOX ) phosphorylation and to investigate the molecular mechanisms involved in this effect "

GM-CSF- ⊣ IL-10: " The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNFalpha induced p47 ( PHOX ) phosphorylation and to investigate the molecular mechanisms involved in this effect "

p47 → TNFalpha: " The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNFalpha induced p47 ( PHOX ) phosphorylation and to investigate the molecular mechanisms involved in this effect "

GM-CSF- ⊣ IL-10: " We found that IL-10 selectively inhibited GM-CSF- but not TNFalpha induced p47PHOX phosphorylation in a concentration dependent manner "

GM-CSF- → TNFalpha: " We found that IL-10 selectively inhibited GM-CSF- but not TNFalpha induced p47PHOX phosphorylation in a concentration dependent manner "

p47PHOX → TNFalpha: " We found that IL-10 selectively inhibited GM-CSF- but not TNFalpha induced p47PHOX phosphorylation in a concentration dependent manner "

p47PHOX → GM-CSF: " As GM-CSF induced p47PHOX phosphorylation is mediated by extracellular signal regulated kinase 1/2 ( ERK1/2 ), we tested the effect of IL-10 on this pathway "

p47PHOX → extracellular signal regulated kinase 1/2: " As GM-CSF induced p47PHOX phosphorylation is mediated by extracellular signal regulated kinase 1/2 ( ERK1/2 ), we tested the effect of IL-10 on this pathway "

ERK1/2 ⊣ IL-10: " We found that IL-10 inhibited GM-CSF induced ERK1/2 activity in an immunocomplex kinase assay "

ERK1/2 → GM-CSF: " We found that IL-10 inhibited GM-CSF induced ERK1/2 activity in an immunocomplex kinase assay "

NADPH oxidase → IL-10: " This IL-10 effect could contribute to the tight regulation of NADPH oxidase activity at the inflammatory site "

Manually curated Databases

No curated data.