IL-6 Rescues Enterocytes from Hemorrhage Induced Apoptosisin Vivoandin Vitroby abcl-2Mediated Mechanism

Abstract

Following a hemorrhagic event, damage to the highly metabolic intestinal tissue induces loss of barrier function leading to bacterial escape and LPS contamination of the host. Orally administered IL-6 restores intestinal barrier function following hemorrhage in both rat and mouse models. IL-6 prevents apoptosis in a variety of lymphoid cells and lines, through the activation of the proto-oncogenebcl-2.This communication elucidates the role of the IL-6–bcl-2interaction in intestinal apoptosis following hemorrhagic shock. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) and p53 immunohistochemical staining were used to examine intestines from mice hemorrhaged and fed saline or IL-6 and enterocytes (IEC-6) exposed to hypoxia and LPS alone or LPS and IL-6in vitro. In situhybridization forbcl-2expression was performed on intestines or enterocytes. Intestinal sections from mice hemorrhaged and fed IL-6 showed reduction in apoptosis and increases inbcl-2gene expression relative to sections taken from mice hemorrhaged and fed saline. IEC-6 cells exposed to hypoxia and LPS had high numbers of TUNEL staining cells. Subsequent exposure to IL-6 after hypoxia and LPS reduced apoptotic cell numbers and increasedbcl-2gene expression. The data show that exposure of intestinal epithelial cells to IL-6 either by oral administration in hemorrhaged mice or by coculture following hypoxia and LPS treatment results in increasedbcl-2gene expression and reduced damage from apoptosis.