Proteomics

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The regulatory roles of Ezh2 in response to lipopolysaccharide (LPS) in macrophages and mice with conditional Ezh2 deletion with LysM-Cre system


ABSTRACT: The responses of macrophages to lipopolysaccharide (LPS) might determine the direction of clinical manifestations of sepsis, which is the immune response against severe infection. Meanwhile, the enhancer of zeste homologue 2 (Ezh2), a histone lysine methyltransferase of epigenetic regulation, might interfere with LPS response. With a single LPS stimulation, Ezh2 null(Ezh2flox/flox; LysM-Crecre/−) macrophages demonstrated lower supernatant TNF-α than Ezh2 control (Ezh2fl/fl; LysM-Cre−/−), perhaps due to an upregulation of Socs3, which is a suppressor of cytokine signaling 3, due to the loss of the Ezh2 gene. In LPS tolerance, Ezh2 null macrophages indicated higher supernatant TNF-α and IL-6 than the control, supporting an impact of the loss of the Ezh2 inhibitory gene. In parallel, Ezh2 null mice demonstrated lower serum TNF-α and IL-6 than the control mice after an LPS injection, indicating a less severe LPS-induced hyper-inflammation in Ezh2 null mice. In conclusion, an absence of Ezh2 in macrophages resulted in less severe LPS-induced inflammation, as indicated by low serum cytokines, with less severe LPS tolerance, as demonstrated by higher cytokine production, partly through the upregulated Socs3.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Jiradej Makjaroen  

LAB HEAD: Asada Leelahavanichkul

PROVIDER: PXD041265 | Pride | 2023-07-20

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
CM_Ezh2_KO_Set1_F.msf Msf
CM_Ezh2_KO_Set1_F1.mgf Mgf
CM_Ezh2_KO_Set1_F1.raw Raw
CM_Ezh2_KO_Set1_F2.mgf Mgf
CM_Ezh2_KO_Set1_F2.raw Raw
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Publications

Less Severe Polymicrobial Sepsis in Conditional <i>mgmt</i>-Deleted Mice Using LysM-Cre System, Impacts of DNA Methylation and MGMT Inhibitor in Sepsis.

Sae-Khow Kritsanawan K   Phuengmaung Pornpimol P   Issara-Amphorn Jiraphorn J   Makjaroen Jiradej J   Visitchanakun Peerapat P   Boonmee Atsadang A   Benjaskulluecha Salisa S   Palaga Tanapat T   Leelahavanichkul Asada A  

International journal of molecular sciences 20230615 12


The O6-methylguanine-DNA methyltransferase (MGMT) is a DNA suicide repair enzyme that might be important during sepsis but has never been explored. Then, the proteomic analysis of lipopolysaccharide (LPS)-stimulated wild-type (WT) macrophages increased proteasome proteins and reduced oxidative phosphorylation proteins compared with control, possibly related to cell injury. With LPS stimulation, <i>mgmt</i> null (<i>mgmt</i><sup>flox/flox</sup>; LysM-Cre<sup>cre/-</sup>) macrophages demonstrated  ...[more]

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