Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis.

摘要: Background & Aims TWEAK, a member of the tumor necrosis factor (TNF) superfamily, promotes intestinal epithelial cell injury and signals through receptor Fn14 following irradiation-induced tissue damage during development colitis in mice. Interleukin (IL)-13, an effector similar models, has been associated with pathogenesis ulcerative (UC). We investigated interactions between TWEAK IL-13 mucosal Methods compared patterns gene expression tissues from wild-type knockout mice γ-irradiation. Intestinal explants these were used to detect induced by TNF-α. Levels messenger RNA for IL-13, measured samples patients UC. Results Based on analysis, mediates γ-irradiation–induced cycle arrest apoptosis. However, alone did not induce or apoptosis primary cells. On other hand, exogenous activated caspase-3 naive explants; this process required Fn14, secretion endogenous TNF-α which was mediated ADAM17. Conversely, activation caspase Fn14. In mucosa UC, levels increased level disease severity. Conclusions IL-13–induced cells requires its (Fn14), TNF-α, could perpetuate aggravate inflammation