Dexamethasone sodium phosphate attenuates lipopolysaccharide-induced neuroinflammation in microglia BV2 cells.
Abnormal neuroinflammation ignited by overproduction of chemokines and cytokines via microglial cells can induce the occurrence and development of neurodegenerative disorders. The aim of this study is to investigate the effects of dexamethasone sodium phosphate (Dex-SP) on chemokine and cytokine secretion in lipopolysaccharide (LPS)-activated microglial cells. LPS markedly enhanced the secretion of pro-inflammatory factors such as regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta-β1 (TGF-β1) and nitric oxide (NO), but decreased the production of macrophage inflammatory protein-1α (MIP-1α) and interleukin 10 (IL-10) in BV-2 microglial cells. Furthermore, LPS increased BV-2 microglial cell migration. However, Dex-SP treatment had the opposite effect, dampening the secretion of RANTES, TGF-β1, and NO, while increasing the production of MIP-1α and IL-10 and blocking migration of LPS-stimulated BV-2 microglial cells. Furthermore, Dex-SP markedly suppressed the LPS-induced degradation of IRAK-1 and IRAK-4, and blocked the activation in TRAF6, p-TAK1, and p-JNK in BV-2 microglial cells. These results showed that Dex-SP inhibited the neuroinflammatory response and migration in LPS-activated BV-2 microglia by inhibiting the secretion of RANTES, TGF-β1, and NO and increasing the production of MIP-1α and IL-10. The molecular mechanism of Dex-SP may be associated with inhibition of TRAF6/TAK-1/JNK signaling pathways mediated by IRAK-1 and IRAK-4.
['Hui|Bin|B|', 'Yao|Xin|X|', 'Zhang|Liping|L|', 'Zhou|Qinhua|Q|']
D000818:Animals D000893:Anti-Inflammatory Agents D002460:Cell Line D002465:Cell Movement D016207:Cytokines D003907:Dexamethasone D007249:Inflammation D018836:Inflammation Mediators D053592:Interleukin-1 Receptor-Associated Kinases D048031:JNK Mitogen-Activated Protein Kinases D008070:Lipopolysaccharides D020930:MAP Kinase Kinase Kinases D051379:Mice D017628:Microglia D015398:Signal Transduction D048029:TNF Receptor-Associated Factor 6
Dexamethasone sodium phosphate Microglia Chemokine Cytokine LPS