Epigenetic Control of Macrophage Polarisation and Soluble Mediator Gene Expression during Inflammation

Figure 2

Histone methylation and acetylation status affect gene expression and macrophage polarisation to the M1 or the M2 phenotype. (a) HMTs induce the secretion of proinflammatory cytokines and chemokines in the cell microenvironment and stabilise the levels of CD14 on the macrophage surface. In contrast, some HMTs suppress the expression of MHC-II and costimulatory molecules and modulate the secretion of proinflammatory mediators. These enzymes contribute significantly to the M2 state, inducing the expression of M2 signature markers and the secretion of anti-inflammatory cytokines. (b) Although histone acetylation by HATs is generically associated with gene expression initiation, HDACs can skew the phenotype of macrophages equally to the M1 or the M2 phenotype. Depending on the HDACs subfamily, these enzymes have been shown to affect proinflammatory/proresolution cytokine secretion, MHC-II and costimulatory molecule expression, secretion of ROS and NO, and control of polarisation-determining TF, arachidonic acid (AA), and 12-hydroxyeicosatetraenoic acid (12-HETE).

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