Impact of <i>Ezh2</i>on macrophage responses against lipopolysaccharide (LPS), experiments on conditional <i>Ezh2</i>deletion mice using LysM-Cre system

Abstract Because the macrophage responses to lipopolysaccharide (LPS) might determine direction of clinical manifestations sepsis (severe infection), impacts enhancer zeste homologue 2 (Ezh2; a histone lysine methyltransferase epigenetic regulation) were explored. The transcriptomic analysis on LPS-activated wild-type macrophages demonstrated an alteration several enzymes. Although Ezh2 silencing, using small interfering RNA (siRNA), in cell line (RAW264.7) indicated non-different LPS between Ezh2-reducing cells and control, higher supernatant TNF-α after twice stimulations (LPS tolerance). With single stimulation, null (Ezh2 flox/flox; LysM-Cre cre/−) lower than control fl/fl; −/−), perhaps due upregulation Socs3 (suppressor cytokine signaling 3; another inhibitor controlled by gene). In tolerance, IL-6 supporting loss inhibitory gene. parallel, mice serum injection (less severe LPS-induced hyper-inflammation) with similar cytokines tolerance (no reduction nddose indicating less conclusion, absence resulted inflammation (higher production), partly, through upregulated Socs3. Supported grants from NSRF via Program Management Unit for Human Resources Institutional Development, Research Innovation (B16F640175 B05F640144). A. K. was supported Second Century Fund (C2F) Postdoctoral Fellowship, Chulalongkorn University.