Interleukin‐10 inhibits lipopolysaccharide‐induced survival and extracellular signal‐regulated kinase activation in human neutrophils

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Lipopolysaccharide (LPS) induces a marked delay in human neutrophil apoptosis that is reversed by the anti‐inflammatory cytokine IL‐10. The effect of IL‐10 is specific since other agents that delay neutrophil apoptosis are not affected. To investigate mechanisms underlying the actions of IL‐10, we examined signaling pathways activated by LPS per se and in response to IL‐10. The MAPK kinase (MEK) 1 inhibitor PD098059, the protein kinase C (PKC) inhibitor Ro31,8220, and the phosphatidylinositol‐3 kinase (PI3‐K) inhibitor LY294002 all partially reversed LPS‐mediated retardation of neutrophil apoptosis, but the p38 MAPK inhibitor SB203850 did not. LPS activates the transcription factor NF‐κB, however, IL‐10 did not affect the ability of LPS to activate NF‐κB as assessed by IκB‐α proteolysis. Although IL‐10 did not alter activation of ERK by GM‐CSF or TNF‐α, it did inhibit activation induced by LPS. Thus our data illustrate that LPS‐induced neutrophil survival is regulated by the MAPK, PKC and PI3‐K pathways as well as NF‐κB, and can be reversed by IL‐10, through a mechanism involving inhibition of ERK activation. Because of the specific nature of this inhibition, we conclude that IL‐10 interferes with an ERK activation pathway, which is not involved in GM‐CSF or TNF‐α signaling.

This publication has 60 references indexed in Scilit: