Nitric oxide and MCP-1 regulation in LPS activated rat Kupffer cells
| Autor: | Pinelopi Manousou, C. Xidakis, George Notas, George Kolios, Vassilis Valatas, Elias A. Kouroumalis |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Kupffer Cells Phosphodiesterase Inhibitors Clinical chemistry Clinical Biochemistry Biology Nitric Oxide Nitric oxide Rats Sprague-Dawley Wortmannin Phosphatidylinositol 3-Kinases Basal (phylogenetics) chemistry.chemical_compound Griess test Internal medicine medicine Animals Secretion Molecular Biology Incubation Cells Cultured Chemokine CCL2 Dose-Response Relationship Drug Liver Diseases Cell Biology General Medicine Macrophage Activation In vitro Rats Androstadienes NG-Nitroarginine Methyl Ester Endocrinology chemistry |
| Zdroj: | Molecular and Cellular Biochemistry. 319:91-98 |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-008-9881-7 |
| Popis: | Nitric oxide (NO) and Monocyte Chemoattractant Protein (MCP)-1 co-regulation has been found in endotoxin-activated macrophages. Kupffer cells (KC) are a main source of soluble-mediators production in liver abnormalities. We investigated in vitro similar co-regulation of NO and MCP-1 production in rat activated KC. Isolated rat KC were cultured in the presence of 1 μg/ml LPS and various concentrations of Wortmannin (0–300 nM), L-NAME (0–500 μM) or MCP-1 (0–100 ng/ml). Production of MCP-1 and NO were measured in supernatants, by ELISA and a modification of the Griess reaction, respectively. Growth arrested KC, stimulated with vehicle, produced a basal amount of NO and MCP-1. In the presence of LPS, cultured KC secreted significantly (P < 0.01) increased amounts of MCP-1 and NO. Pre-treatment of KC with various concentrations of L-NAME significantly (P < 0.05) reduced the LPS-induced secretion of NO in a concentration dependent manner, but the MCP-1 production remained unaffected. Pre-treatment with Wortmannin significantly (P < 0.05) inhibited LPS-induced secretion of MCP-1 and NO in a concentration dependent manner. Linear regression analysis revealed a positive correlation between MCP-1 and NO in the LPS (r = 0.59171, P < 0.0001) and Wortmannin (r = 0.9215, P = 0.009) treated groups, but not in the L-NAME (r = −0.08513, P = 0.873). Incubation of KC with various concentrations of MCP-1 did not increase the NO production. These results indicate that KC might be the main source of NO and MCP-1 production in liver disorders, probably through the induction of PI3-kinase(s) and without any co-regulation between these molecules, which might represent two independent immunoregulatory pathways in the role of KC in hepatic disorders. |
| Databáze: | OpenAIRE |
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