Kasper SH Spalinger MR Raselli T Scharl M 2015 BACKGROUND/AIMS Genetic polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) have been associated with inflammatory bowel disease (IBD). A recent study demonstrated that PTPN2 regulates ER stress signalling in pancreatic β-cells. Therefore, we investigated whether PTPN2 regulates ER stress pathways, apoptosis and cytokine secretion in human intestinal epithelial cells (IECs) and monocytes. METHODS THP-1 and HT-29 IECs were stimulated with 2 µg/ml tunicamycin (TNM) for the indicated periods of time. For knockdown experiments, cells were transfected using a mixture of three different PTPN2-specific siRNA oligonucleotides. Cell lysates were analysed by Western blot and real-time PCR. Cytokine secretion was studied by ELISA measurements of cell culture supernatant. RESULTS TNM treatment reduced PTPN2 protein levels in HT-29 IECs and THP-1 monocytes. Knockdown of PTPN2 in THP-1 monocytes led to an exaggerated induction of phospho-eIF2α, enhanced PARP cleavage, indicative of apoptosis, and attenuated IL-8 and TNF secretion upon TNM stimulation. In HT-29 cells PTPN2 deficiency caused reduced phosphorylation of eIF2α and PARP cleavage under ER stress conditions. CONCLUSIONS Whereas the knockdown of PTPN2 made THP-1 cells more susceptible to ER stress, PTPN2 deficiency reduced ER stress responses in HT-29 IECs. This suggests that PTPN2 regulates adaptation to ER stress in a cell type-specific manner. https://sonar.ch/global/documents/211989 eng info:eu-repo/semantics/altIdentifier/doi/10.1159/000375459 info:eu-repo/semantics/altIdentifier/pmid/25823847 Digestion. - 2015 Anti-Bacterial Agents Apoptosis Blotting, Western Cytokines Endoplasmic Reticulum Stress Epithelial Cells Eukaryotic Initiation Factor-2 Gene Knockdown Techniques HT29 Cells Humans Interleukin-8 Intestinal Mucosa Monocytes Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 2 Proto-Oncogene Proteins RNA, Small Interfering Real-Time Polymerase Chain Reaction Signal Transduction Tumor Necrosis Factor-alpha Tunicamycin A cell type-specific role of protein tyrosine phosphatase non-receptor type 2 in regulating ER stress signalling. http://purl.org/coar/resource_type/c_6501