P040 Protein tyrosine phosphate non receptor type 22 regulates muramyl-dipeptide induced effects in human monocytes

Abstract

microscopy. Rat ileal and colonic mucosae were mounted to Ussing chambers and exposed basolaterally to IL-22. The effect of IL-22 on mobility on intestinal epithelial cells was determined in cell culture-based models for wound-healing as well as epithelial invasion. Epithelial polarity was examined in 3-dimensional Caco-2 cysts, grown in matrigel. Results: IL-22 induced a significant and dose-dependent (1, 10, 100 ng/ml) reduction in Rt in both, Caco-2 and HT-29 cells, which was abolished by inhibition of PI-3 kinase and MAP kinase, but not by STAT inhibitors. Paracellular passage of biotin was elevated accordingly. In IL-22 treated rat ileum and colon complex changes including the subepithelial layer were found, indicating either protective or pro-inflammatory changes according to the concentration used. Preliminary data revealed a dose dependent reduction of the mucosal surface area in ileal and colonic specimen. IL-22-mediated epithelial wound healing was confirmed in the HT-29 model. Furthermore, epithelial invasion was dramatically increased in IL-22-treated intestinal epithelial cells. On the other hand, epithelial apoptosis was also modestly increased. The TJ proteins ZO-1 and JAM-A localized to intracellular pools and not to TJs. Caco-2 matrigel cysts displayed an increase in multiple lumen, atypical mitoses and basal actin protrusions. Conclusions: By reducing epithelial polarity, IL-22 reprograms intestinal epithelia to gain migratory/invasive properties and at the same time to lose barrier properties. This has implications not only for wound healing but also for inflammation-associated carcinogenesis.