IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism.
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-oncogene bcl-2. This communication elucidates the role of the IL-6-bcl-2 interaction 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-6 in vitro. In situ hybridization for bcl-2 expression was performed on intestines or enterocytes. Intestinal sections from mice hemorrhaged and fed IL-6 showed reduction in apoptosis and increases in bcl-2 gene 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 increased bcl-2 gene 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 increased bcl-2 gene expression and reduced damage from apoptosis.
Rollwagen
F M
FM
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20814-4799, USA. frollag@usuhs.mil
Yu
Z Y
ZY
Li
Y Y
YY
Pacheco
N D
ND
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006471:Gastrointestinal Hemorrhage / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000494:pharmacology*; D007422:Intestines / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D011994:Recombinant Proteins