Differential signaling mechanisms of HNP-induced IL-8 production in human lung epithelial cells and monocytes.

摘要: Human neutrophil peptides (HNP) kill microorganisms but also modulate immune responses through upregulation of the chemokine IL-8 by activation nucleotide P2Y(6) receptor. However, intracellular signaling mechanisms remain yet to be determined. lung epithelial cells (A549) and monocytes (U937) were stimulated with HNP in absence presence specific kinase inhibitors for Src, extracellular signal-regulated kinase-1 -2 (ERK1/2), p38 mitogen-activated protein (MAPK), c-Jun-N-terminal kinases (JNK), Akt. induced a rapid phosphorylation both cell types associated dose-dependent, selective production among 10 cytokines assayed. The HNP-induced was blocked Src tyrosine inhibitor PP2, MEK1/2 U0126, phosphatidylinositol 3 (PI3K) LY294002, not JNK SP600125 types. Treatment SB203580 attenuated only monocytes. Blockade blunted ERK1/2 Akt In contrast, inhibition had no effect on other cells. We conclude that PI3K/Akt pathways is required release which occurs Src-independent manner cells, while Src-dependent