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Differential signaling mechanisms of HNP‐induced IL‐8 production in human lung epithelial cells and monocytes
Author(s) -
Syeda Farisa,
Liu HuiYu,
Tullis Elizabeth,
Liu Mingyao,
Slutsky Arthur S.,
Zhang Haibo
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21279
Subject(s) - proto oncogene tyrosine protein kinase src , protein kinase b , microbiology and biotechnology , kinase , ly294002 , p38 mitogen activated protein kinases , phosphorylation , chemistry , cancer research , tyrosine protein kinase csk , mitogen activated protein kinase , biology , mapk/erk pathway , sh3 domain
Human neutrophil peptides (HNP) kill microorganisms but also modulate immune responses through upregulation of the chemokine IL‐8 by activation of the nucleotide P2Y 6 receptor. However, the intracellular signaling mechanisms remain yet to be determined. Human lung epithelial cells (A549) and monocytes (U937) were stimulated with HNP in the absence and presence of the specific kinase inhibitors for Src, extracellular signal‐regulated kinase‐1 and ‐2 (ERK1/2), p38 mitogen‐activated protein kinase (MAPK), c‐Jun‐N‐terminal kinases (JNK), and Akt. HNP induced a rapid phosphorylation of the kinases in both cell types associated with a dose‐dependent, selective production of IL‐8 among 10 cytokines assayed. The HNP‐induced IL‐8 production was blocked by the Src tyrosine kinase inhibitor PP2, MEK1/2 inhibitor U0126, and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002, but not by the JNK inhibitor SP600125 in both cell types. Treatment with the p38 inhibitor SB203580 attenuated the HNP‐induced IL‐8 production only in monocytes. Blockade of Src kinase blunted HNP‐induced phosphorylation of the ERK1/2 and Akt but not p38 in monocytes. In contrast, Src inhibition had no effect on phosphorylation of the other kinases in the lung epithelial cells. We conclude that the activation of ERK1/2 and PI3K/Akt pathways is required for HNP‐induced IL‐8 release which occurs in a Src‐independent manner in lung epithelial cells, while is Src‐dependent in monocytes. J. Cell. Physiol. 214: 820–827, 2008. © 2007 Wiley‐Liss, Inc.