title: Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.
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-6RΔIECmice) did not display increased susceptibility to acute dextran sulfate sodium (DSS)-induced colitis. In the azoxymethane DSS model IL-6RΔIECmice 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.
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|First Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Aden
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Breuer
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rehman
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Geese
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Tran
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sommer
authors.affiliation: CONARIS Research Institute AG, Kiel, Germany.
authors.forename: G H
authors.initials: GH
authors.lastname: Waetzig
authors.affiliation: Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: T M
authors.initials: TM
authors.lastname: Reinheimer
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|First Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Institute of Biochemistry, Kiel University, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rose-John
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Scheller
authors.affiliation: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Rosenstiel