Elevated apoptosis of intestinal epithelial cells (IECs) greatly impairs the epithelial barrier integrity and contributes to the pathogenesis of Crohn's Disease (CD). Overproduction of pro-inflammatory cytokine Interferon-γ (IFN-γ) induces the excessive apoptosis of IECs and is involved in CD development. PRDM5 (PR domain containing 5 PFM2) a member of PRDM family, reportedly acts as a transcriptional regulator involved in tissue specific differentiation and tumor development. In this study, we investigated PRDM5 expression and its potential functions in both human CD (Crohn's disease) and TNBS (2,4,6-trinitrobenzenesulfonic acid sol)-induced mice experimental colitis. As shown by western blot and immunohistochemistry, significant up-regulation of PRDM5 was found in the inflamed intestinal tissues of CD patients and TNBS-treated mice, and the molecule was mainly located in IECs. To explore the biological functions of PRDM5 in IEC apoptosis, we established the interferon-γ (IFN-γ) induced cellular apoptosis model on human IEC line HT29 in vitro. IFN-γ significantly increased the expression of PRDM5 in a both time-dependent and concentration-dependent manner in HT29 cells, which was accompanied with an up-regulated expression of apoptotic markers (active caspase-3 and cleaved PARP(poly (ADP-ribpse) polymerase)). Inhibiting PRDM5 expression by siRNA attenuated the IFN-γ-triggered accumulation of active caspase-3 and cleaved PARP in IECs. Moreover, flow cytometry assay and CCK-8 analysis revealed that PRDM5 knockdown significantly alleviated the IFN-γ-induced cellular apoptosis in HT29 cells. Taken together, these data suggest that highly expressed PRDM5 may promote the IFN-γ-induced IEC apoptosis in the progression of CD.
Keywords: Apoptosis; Crohn’s disease; IFN-γ; Intestinal epithelial cells; PRDM5.
Copyright © 2016 Elsevier GmbH. All rights reserved.