HDAC1 and HDAC2 control the intestinal epithelial cell inflammatory response

Histone deacetylase inhibitors (HDACi) modulate the intestinal epithelial cell inflammatory and the ER stress responses. Little is known of the role of specific HDACs in these responses. We thus investigated the role of HDAC1. Methods IEC‐6 rat intestinal epithelial cells were depleted in HDAC1 by infection with a lentiviral vector expressing a shRNA against HDAC1. Cell proliferation was measured. HDAC1 and HDAC2 levels were determined by western blot and semi‐quantitative RT‐PCR. Protein levels of CHOP, a marker of ER stress, were determined by western blot after ER stress induction with tunicamycin. Inflammatory gene expression after IL‐1beta treatment was assessed by semi‐quantitative RT‐PCR. Results Reduced HDAC1 protein levels led to HDAC2 protein increases and to decreased cell proliferation. CHOP protein levels were reduced in HDAC1‐null IEC‐6 cells as opposed to control cells, in response to ER stress. HDAC1 depletion led to gene‐specific modifications of the pattern of expression of inflammatory genes in response to IL‐1beta. Indeed, one class of genes displayed decreased basal levels with normal IL‐1beta induction levels, while another showed both increased basal and IL‐1beta‐stimulated levels. Conclusion Loss of HDAC1 in IEC‐6 cells may uncover specific roles for both HDAC1 and HDAC2 in the control of the intestinal epithelial cell inflammatory response. Supported by CCFC.