期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 316, 期 -, 页码 17-22出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2017.12.005
关键词
M2 microglia polarization; Exenatide; GLP-1 receptor; cAMP/PKA; p38 beta MAPK; CREB
资金
- National Natural Science Foundation of China [81374000, 81673403]
- Shanghai Industrial Translational Project [15401901300]
GLP-1 receptor agonists, exenatide and GLP-1, promoted M2 type polarization in monocytes/macrophages and microglial cells. This study explored the signal basis underlying exenatide-stimulated expression of M2 microglia-specific genes, including the cytoplasmic marker Arg 1, surface marker CD206, and secretion protein marker IL-4. Treatment with exenatide in cultured primary microglial cells concentration dependently stimulated the expression of Arg 1, CD206 and IL-4, but did not significantly alter LPS-stimulated expression of TNF-alpha, IL-1 beta and IL-6. The stimulatory effects of exenatide were completely prevented by the GLP-1 receptor antagonist exendin(9-39), but not altered by application of LPS. Furthermore, the adenylyl cyclase inhibitor DDA, PKA inhibitor H89 and CREB inhibitor KG501 completely blocked exenatide-induced overexpression of Arg 1, CD206 and IL-4. In addition, exenatide-stimulated expression of Arg 1 and CD206 was totally blocked by the p38 MAPK inhibitor SB203580 and gene silencer siRNA/p38 beta (but not siRNA/p38 alpha), whereas the expressed IL-4 was not significantly altered by the p38 inhibitor or other MAPK subtype inhibitors. These findings revealed that both classic Gs-cAMP/PKA/CREB and alternative Gs-cAMP/PKA/p38 beta/CREB mediated GLP-1 receptor agonism-induced overexpression of M2 microglial biomarkers.
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