| The colonic epithelium is a dynamic tissue that provides a barrier between immune cells in the lamina propria and luminal microbes. Injury to this barrier stimulates the upregulation of pro-apoptotic cytokines associated with inflammatory responses, thus hindering the ability of epithelial cells to heal the wound. The colonic epithelial cell line HT-29 was used to examine the effects of PAR2 signalling on cellular proliferation and survival. Activation of PAR2 did not stimulate proliferation and was associated with transient ERK1/2 MAPK, as well as PI3K, activity. On the other hand, PAR2 signalling decreased IFNgamma/TNFalpha-induced apoptosis in HT-29 cells as determined by decreased cleavage of caspase-8, caspase-3 and PARP as well as decreased externalization of phosphatidylserine. Finally, knockdown of PAR2 sensitized HT-29 cells to IFNgamma/TNFalpha- induced apoptosis and blocked the survival response. Serine proteinase capable of activating PAR2 may aid in healing of the colonic mucosa after injury by enhancing epithelial survival. |
