Prostaglandin I2 analogue, iloprost, down regulates mitogen-activated protein kinases of macrophages
| Autor: | Minjuan Fu, F.Rosa Lo, Chong-Jeh Lo |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
MAPK/ERK pathway
Lipopolysaccharides Male medicine.medical_specialty p38 mitogen-activated protein kinases Blotting Western Pharmacology Biology Proinflammatory cytokine Cell Line Mice Internal medicine Macrophages Alveolar medicine Escherichia coli Animals Iloprost Protein kinase A Kinase Tumor Necrosis Factor-alpha Macrophages Endothelial stem cell Enzyme Activation Endocrinology Calcium-Calmodulin-Dependent Protein Kinases lipids (amino acids peptides and proteins) Surgery Tumor necrosis factor alpha Rabbits medicine.drug |
| Zdroj: | The Journal of surgical research. 76(2) |
| ISSN: | 0022-4804 |
| Popis: | Objective. Vascular endothelial cells (EC) play a pivotal role in diffuse organ injury seen in ARDS and MOFS. On exposure to cytokines or endotoxin (LPS), EC are stimulated to express adhesion molecules as well as proinflammatory and procoagulant activity. However, the potential feedback control of EC on macrophages (Mφ) is not clear. We studied the cellular mechanism of iloprost, a PGI 2 analogue, in regulation of TNF production by LPS-stimulated Mφ. Methods. Rabbit alveolar Mφ and mouse Mφ RAW 264.7 cells were exposed to Escherichia coli LPS in the presence of various concentrations of iloprost. TNF production was measured by L929 bioassays. To further study the cellular mechanism of iloprost on Mφ activation, RAW 264.7 cells were stimulated by LPS (10 μg/ml) in the presence of either iloprost or specific mitogen-activated protein kinase (MAPK) inhibitors, either PD98059 or SB202190. P44/P42 and P38 MAPK activation were evaluated by Western blot assays with anti-phospho MAPK antibodies. Results. LPS induced Mφ TNF production, which was inhibited by iloprost. Iloprost also attenuated the activation of P44/P42 and P38 induced by LPS. Inhibition of P44/P42 with PD98059 or P38 with SB202190 significantly reduced TNF production by LPS-stimulated RAW cells. Conclusions. The regulatory mechanism of EC on Mφ activation is dependent on PGI 2 . The effect of PGI 2 on Mφ is, at least in part, mediated through inhibiting MAPKs. |
| Databáze: | OpenAIRE |
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