Selective activation of STAT3 in human monocytes stimulated by G-CSF: implication in inhibition of LPS-induced TNF-α production
| Autor: | Noriko Kamata, Akiko Kimura-Eto, Erina Sakamoto, Taro Hasegawa, Fumihiko Hato, Masayuki Hino, Saori Nishiki, Seiichi Kitagawa |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor MAPK/ERK pathway medicine.medical_specialty Lipopolysaccharide MAP Kinase Signaling System Neutrophils Physiology medicine.medical_treatment Biology Monocytes chemistry.chemical_compound Proto-Oncogene Proteins Internal medicine Granulocyte Colony-Stimulating Factor medicine Extracellular Humans Enzyme Inhibitors Phosphorylation Cells Cultured Feedback Physiological Tumor Necrosis Factor-alpha Monocyte Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases Molecular biology Interleukin-10 DNA-Binding Proteins Interleukin 10 medicine.anatomical_structure Endocrinology Cytokine chemistry Receptors Granulocyte Colony-Stimulating Factor Trans-Activators Tumor necrosis factor alpha Signal transduction Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 286:C1302-C1311 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Lipopolysaccharide (LPS) induced tumor necrosis factor (TNF)-α production in human monocytes, which was dependent on activation of extracellular signal-regulated kinase (ERK), p38, c-Jun NH2-terminal kinase (JNK), and nuclear factor (NF)-κB. LPS-induced TNF-α production was inhibited by granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-10. G-CSF, like IL-10, exerted the inhibitory effect even when simultaneously added with LPS. Among the signaling pathways, signal transducer and activator of transcription 3 (STAT3) was selectively activated in monocytes stimulated by G-CSF or IL-10. G-CSF-mediated inhibition of LPS-induced TNF-α production as well as G-CSF-induced STAT3 phosphorylation and suppressor of cytokine signaling 3 mRNA expression were prevented by pretreatment of monocytes with AG-490, an inhibitor of Janus kinase 2. G-CSF did not affect LPS-induced activation of ERK, p38, JNK, and NF-κB, indicating that G-CSF affects the pathway downstream or independently of these signaling molecules. G-CSF-induced, but not IL-10-induced, STAT3 phosphorylation was attenuated in the presence of LPS. These findings suggest that G-CSF, like IL-10, inhibits LPS-induced TNF-α production in human monocytes through selective activation of STAT3, and the immunomodulation observed in vivo by G-CSF administration may be partly ascribed to the direct effect of G-CSF on monocyte functions. |
| Databáze: | OpenAIRE |
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