Figure 6. Working model of HDAC inhibitor-mediated suppression of ERK and JNK phosphorylation and inflammatory gene expression.
A) HDAC 2 regulates TNFα-induced ERK signaling. HDACs 1 and 2 in combination regulate TNFα-induced JNK phosphorylation. Inhibition of ERK and JNK partly explain anti-inflammatory mechanisms linked to class I selective HDAC inhibitors in bovine mammary epithelial cells (MAC-Ts). B) In addition, inhibition of HDACs attenuates pro-inflammatory gene expression through mechanisms associated with canonical regulation of gene expression, independent of MAPK signaling.