Interfering with interferon-γ signalling in intestinal epithelial cells: selective inhibition of apoptosis-maintained secretion of anti-inflammatory interleukin-18 binding protein

摘要: The intestinal epithelial barrier represents an important component in the pathogenesis of inflammatory bowel diseases. Interferon (IFN)-γ, a T helper type 1 (Th1) cytokine, regulated by interleukin (IL)-18/IL-18 binding protein (bp) system, modulates integrity this barrier. aim work was to study functionally consequences IFN-γ on cells (IEC) and interfere selectively with identified adverse effects. IEC lines were stimulated IFN-γ. IL-18 IL-18bp assessed enzyme-linked immunosorbent assay. Staining phosphatidylserine, DNA laddering, lactate dehydrogenase (LDH) release, cleavage poly-adenosine diphosphate-ribose-polymerase (PARP) activation caspase-3 analysed determine cell death. Inhibitors tyrosine kinase, or p38 mitogen-activated kinase ((MAP) activity used. Cytokines measured supernatants colonic biopsies healthy controls disease (IBD) patients. In lines, up-regulated selectively. Ex vivo, present from cultured inflammation. Contrary previous reports, alone induced apoptosis as demonstrated phosphatidylserin staining, LDH release. Further, caspase-3, PARP expression pro-apoptotic Bad induced. Partial inhibition but not JAK preserved up-regulation expression. Selective mediated apoptosis, while preserving its beneficial ratio IL-18/IL-18bp, could contribute mucosal