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PI3Kγ mediates microglial proliferation and cell viability via ROS

Abstract: (1) Background: Rapid microglial proliferation contributes to the complex responses of the innate immune system in the brain to various neuroinflammatory stimuli. Here, we investigated the regulatory function of phosphoinositide 3-kinase γ (PI3Kγ) and reactive oxygen species (ROS) for rapi...

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Main Authors: Schmidt, Caroline (Author) , Schneble, Nadine (Author) , Lajqi, Trim (Author) , Wetzker, Reinhard (Author) , Müller, Jörg (Author) , Bauer, Reinhard (Author)
Format: Article (Journal)
Language:English
Published: 24 September 2021
In: Cells
Year: 2021, Volume: 10
ISSN:2073-4409
DOI:10.3390/cells10102534
Online Access:Verlag, kostenfrei: https://doi.org/10.3390/cells10102534
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Author Notes:Caroline Schmidt, Nadine Schneble-Löhnert, Trim Lajqi, Reinhard Wetzker, Jörg P. Müller and Reinhard Bauer

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520 |a Abstract: (1) Background: Rapid microglial proliferation contributes to the complex responses of the innate immune system in the brain to various neuroinflammatory stimuli. Here, we investigated the regulatory function of phosphoinositide 3-kinase γ (PI3Kγ) and reactive oxygen species (ROS) for rapid proliferation of murine microglia induced by LPS and ATP. (2) Methods: PI3Kγ knockout mice (PI3Kγ KO), mice expressing catalytically inactive PI3Kγ (PI3Kγ KD) and wild-type mice were assessed for microglial proliferation using an in vivo wound healing assay. Additionally, primary microglia derived from newborn wild-type, PI3Kγ KO and PI3Kγ KD mice were used to analyze PI3Kγ effects on proliferation and cell viability, senescence and cellular and mitochondrial ROS production; the consequences of ROS production for proliferation and cell viability after LPS or ATP stimulation were studied using genetic and pharmacologic approaches. (3) Results: Mice with a loss of lipid kinase activity showed impaired proliferation of microglia. The prerequisite of induced microglial proliferation and cell viability appeared to be PI3Kγ-mediated induction of ROS production. (4) Conclusions: The lipid kinase activity of PI3Kγ plays a crucial role for microglial proliferation and cell viability after acute inflammatory activation. Keywords: phosphoinositide 3-kinase γ; proliferation; cell viability; microglia; ROS; LPS; ATP 
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