Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.

Authors:
K Aden, A Breuer, A Rehman, H Geese, F Tran, J Sommer, G H Waetzig, T M Reinheimer, S Schreiber, S Rose-John, J Scheller, P Rosenstiel
Year of publication:
2016
Volume:
5
Issue:
11
Issn:
2157-9024
Journal title abbreviated:
Oncogenesis
Journal title long:
Oncogenesis
Abstract: 
Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling. Mice deficient in intestinal IL-6R (IL-6R(ΔIEC) mice) did not display increased susceptibility to acute dextran sulfate sodium (DSS)-induced colitis. In the azoxymethane DSS model IL-6R(ΔIEC) mice were not protected from inflammation-induced carcinogenesis but showed comparable tumor load to wild-type mice. These data indicate that classic signalling is not the major pathway to transduce IL-6 stimuli into the intestinal epithelium.