Differential signaling mechanisms of HNP-induced IL-8 production in human lung epithelial cells and monocytes
| Autor: | Mingyao Liu, Farisa Syeda, Hui-Yu Liu, Haibo Zhang, Elizabeth Tullis, Arthur S. Slutsky |
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| Rok vydání: | 2007 |
| Předmět: |
alpha-Defensins
MAP Kinase Signaling System Physiology p38 mitogen-activated protein kinases Clinical Biochemistry Biology Article Monocytes Phosphatidylinositol 3-Kinases chemistry.chemical_compound Humans LY294002 Protein kinase A Lung Protein kinase B Cells Cultured Dose-Response Relationship Drug Kinase Interleukin-8 Epithelial Cells Cell Biology Cell biology Enzyme Activation src-Family Kinases chemistry Phosphorylation Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Cellular Physiology. 214:820-827 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.21279 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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