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- W1960380143 abstract "Macrophages respond to environmental cues by changing gene expression to assume different states of activation. The activator-dependent states include M1, induced by LPS and IFNγ and M2, induced by IL-4 and IL-13. Macrophages exist in a full spectrum of states of activation between M1 and M2. M1 macrophages produce inflammatory cytokines whereas M2 macrophages produce anti-inflammatory IL-10 and TGFβ. A variety of transcription factors regulate transcription programs that control M1/M2 polarization. Recent findings indicate that IL-4 induces KLF4 via activation of STAT6. KLF4 and STAT6 induce each other and cooperatively induce M2 markers. Transcription factors must use catalytic proteins to implement their biological functions. We discovered that KLF4 induce a novel zinc finger protein with dual catalytic activities, called MCPIP, which mediates M2 polarization. The role of MCPIP in vivo was demonstrated with macrophages from mice with myeloid cell targeted knockout or over expression of MCPIP. ROS production, ER stress and autophagy, required for M2 polarization, was sequentially induced by MCPIP expression in murine macrophages. With MCPIP mutants, that have only ubiquitinase activity or RNase activity, it was demonstrated that both catalytic activities are involved in M2 polarization. MCPIP modulation of the miRome and ubiquitome involved in macrophage polarization remains obscure. Involvement of macrophage polarization in many major diseases suggest the possibilities of novel therapeutics that can modulate MCPIP functions to control macrophage polarization." @default.
- W1960380143 created "2016-06-24" @default.
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- W1960380143 date "2015-10-27" @default.
- W1960380143 modified "2023-09-27" @default.
- W1960380143 title "Macrophage: How the Chameleon Responds to the Environment?" @default.
- W1960380143 doi "https://doi.org/10.14800/macrophage.927" @default.
- W1960380143 hasPublicationYear "2015" @default.
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