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• W2074306506 abstract "Abstract Accumulating evidence indicates that activated microglia contribute to the neuropathology involved in many neurodegenerative diseases and after traumatic injury to the CNS . The cytokine transforming growth factor‐beta 1 ( TGF ‐β1), a potent deactivator of microglia, should have the potential to reduce microglial‐mediated neurodegeneration. It is therefore perplexing that high levels of TGF ‐β1 are found in conditions where microglia are chronically activated. We hypothesized that TGF ‐β1 signaling is suppressed in activated microglia. We therefore activated primary rat microglia with lipopolysaccharide ( LPS ) and determined the expression of proteins important to TGF ‐β1 signaling. We found that LPS treatment decreased the expression of the TGF ‐β receptors, TβR1 and TβR2, and reduced protein levels of Smad2, a key mediator of TGF ‐β signaling. LPS treatment also antagonized the ability of TGF ‐β to suppress expression of pro‐inflammatory cytokines and to induce microglial cell death. LPS treatment similarly inhibited the ability of the TGF ‐β related cytokine, Activin‐A, to down‐regulate expression of pro‐inflammatory cytokines and to induce microglial cell death. Together, these data suggest that microglial activators may oppose the actions of TGF ‐β1, ensuring continued microglial activation and survival that eventually may contribute to the neurodegeneration prevalent in chronic neuroinflammatory conditions. image We propose that LPS/TLR4 signaling interferes with key components in the TGF‐β1 signaling pathway in primary microglia. As a result, the ability of TGF‐ β1 to exert anti‐inflammatory effects is significantly reduced leading to prolonged survival of classically activated microglia. Identifying the mechanisms by which TGF‐ β1 signaling is targeted during microglia activation may yield novel strategies for deactivating chronically activated microglia." @default.
• W2074306506 created "2016-06-24" @default.
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• W2074306506 date "2013-12-17" @default.
• W2074306506 modified "2023-10-16" @default.
• W2074306506 title "LPS antagonism of TGF-β signaling results in prolonged survival and activation of rat primary microglia" @default.
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• W2074306506 doi "https://doi.org/10.1111/jnc.12612" @default.
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