Exenatide (a GLP-1 agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner
| Autor: | Łukasz Bułdak, Aleksandra Bołdys, Grzegorz Machnik, Marcin Basiak, Krzysztof Łabuzek, Belowski D, Rafał J. Bułdak, Bogusław Okopień |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_specialty Interleukin-1beta Anti-Inflammatory Agents Nitric Oxide Synthase Type II Inflammation Monocytes Proinflammatory cytokine 03 medical and health sciences Glucagon-Like Peptide 1 Internal medicine medicine Humans Protein kinase A Protein kinase B Cells Cultured Pharmacology business.industry Kinase Tumor Necrosis Factor-alpha Venoms Macrophages General Medicine Cyclic AMP-Dependent Protein Kinases Interleukin-10 Interleukin 10 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Exenatide Tumor necrosis factor alpha medicine.symptom business Peptides Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Pharmacological reports : PR. 68(2) |
| ISSN: | 2299-5684 |
| Popis: | Background Incretin-based therapies in the treatment of type 2 diabetes mellitus are associated with significant improvements in glycemic control, which are accompanied by a beneficial impact on atherosclerosis. Macrophages are essential in the development of atherosclerotic plaques and may develop features that accelerate atherosclerosis (classically activated macrophages) or protect arterial walls against it (alternatively activated macrophages). Therefore, we explored whether beneficial actions of exenatide are connected with the influence on the macrophages’ phenotype and synthesis of inflammatory and anti-inflammatory cytokines. Methods Monocytes/macrophages were harvested from 10 healthy subjects. Cells were cultured in the presence of exenatide, exendin 9-39 (GLP-1 antagonist), LPS, IL-4, PKI (PKA inhibitor) and triciribine (PKB/Akt inhibitor). We measured the effects of the above-mentioned compounds on markers of macrophages’ phenotype (inducible nitrous oxide (iNOS), arginase 1 (arg1) and mannose receptors) and concentration of nitrite, IL-1β, TNF-α and IL-10. Results Exenatide significantly increased the level of IL-10 and decreased both TNF-α and IL-1β in LPS-treated monocytes/macrophages. Furthermore exenatide increased the expression of arg1–a marker of classical activation and reduced the LPS-induced expression of iNOS–a marker of classical activation. According to experiments with protein kinases inhibitors we found that proinflammatory markers were protein kinase A dependent, whereas the activation of alternative activation was similarly reliant on protein kinase A and B/Akt. Conclusions We showed that exenatide skewed the macrophages phenotype toward anti-inflammatory phenotype and this effect is predominantly attributable to protein kinase A and to a less extent to B/Akt activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink