Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling

Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways

“…LPS-induced proinflammatory cytokine production was performed using cultured microglial cells according to a previously described method [ 28 ]. To investigate the influence of TNFα on LPS-induced microglial activation, BV2 cells were treated with different concentrations of LPS for 12 h and analyzed by an established Enzyme-Linked Immunosorbent Assay (ELISA) assay.…”

“…Several studies have suggested that the up-regulation of TNFα, IL1β, IL6, and COX2 plays important roles in many inflammatory diseases including cytotoxicity in brain injuries and many neurodegenerative diseases such as AD, PD, and prion diseases [ 5 , 43 , 44 ]. Thus, many studies have been conducted to find their inhibitors [ 9 , 14 , 15 , 17 , 28 , 31 , 32 ]. Our results showed that APM reduced the expression of TNFα, IL1β, IL6, and COX2 by blocking their expression in LPS-stimulated BV2 and rat primary microglial cells.…”

“…Microglia can recognize pathogen-associated molecular patterns through TLR pattern recognition receptors expressed on the cell surface [ 46 ]. TLR4 is known to recruit adapter molecules, and LPS mediates immune activation [ 28 ]. CaMKII promotes the production of TLR-triggered proinflammatory cytokines in macrophages [ 47 ].…”

“…The potential involvement of NF-κB and STAT3 was investigated because the promoters of both TNFα and IL-6 contain binding sites for NF-κB and STAT3, which are known to be involved in neurological disorders associated with increased inflammation [ 11 , 32 , 48 ]. Recently, several studies have reported that the cell signaling control of these transcription factors inhibits neuroinflammation [ 13 , 14 , 15 , 17 , 28 ]. Our previous studies reported anti-inflammatory effects in dopaminergic neurons, mesencephalic neurons, and BV2 microglial cells through the strong inhibition of NF-κB and STAT3 translocation [ 19 ].…”

“…MAPK-ERK signaling is associated with LPS-induced immune responses via SK channels and TLR4 signaling [ 3 , 28 , 30 ]. In addition, this signaling maintains NF-κB and STAT3 signaling in microglia [ 17 , 19 ].…”