IL-6-driven FasL promotes NF-?Bp65/PUMA-mediated apoptosis in portal hypertensive gastropathy.

ABSTRACT: Mucosal epithelial apoptosis with non-specific inflammation is an essential pathological characteristic in portal hypertensive gastropathy (PHG). However, whether a coordinated crosstalk between myeloid cells and epithelial cells involved in PHG remains unclear. IL-6, which is induced in the mucosa of PHG patients and mice, promotes FasL production via enhancing NF-?Bp65 activation in myeloid cells, while blockage of IL-6 signaling by Tocilizumab or deletion of NF-?Bp65 in myeloid cells attenuates the inflammatory response and Fas/FasL-mediated epithelial apoptosis in PHG. IL-6-driven FasL from myeloid cells combines with epithelial Fas receptor to encourage NF-?Bp65/PUMA-mediated epithelial apoptosis in PHG, and inhibition of NF-?Bp65 or knockout of PUMA alleviates Fas/FasL-mediated epithelial apoptosis in PHG. These results indicate that IL-6 drives FasL generation via NF-?Bp65 in myeloid cells to promote Fas/NF-?Bp65/PUMA-mediated epithelial apoptosis in PHG, and this coordinated crosstalk between myeloid cells and epithelial cells may provide a potential therapeutic target for PHG.

SUBMITTER: Tan S 

PROVIDER: S-EPMC6776649 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature