title: IL-15 protects intestinal epithelial cells.
abstract: IL-15, a T-cell growth factor, has been shown to be increased in inflammatory bowel disease (IBD). It has been suggested that neutralization of IL-15 could protect from T cell-dependent autoimmune inflammation. On the other hand, an anti-apoptotic effect of IL-15 has been demonstrated in kidney epithelial cells during nephritis. We therefore tested the role of IL-15 in two different experimental models of colitis in vivo, and in models of intestinal epithelial cell (IEC) apoptosis in vitro. IL-15 blockade in chronic dextran sulphate sodium-induced colitis resulted in aggravation of the disease with a significantly 2.1-fold increased epithelial damage score compared to controls. TUNEL staining clearly revealed increased apoptosis. IL-6, TNF and IFN-gamma secretion by mesenteric lymph node cells were increased. In the T cell-dependent SCID transfer model of colitis IL-15 neutralization reduced the inflammatory infiltration and proinflammatory cytokine production. Despite that, the intestinal epithelial damage was not reduced. In vitro, IL-15 pre-incubation prevented up to 75% of CH11 antibody-induced apoptosis in SW-480 cells and reduced caspase-3 activity. According to this, endogenously produced IL-15 in chronic colitis does not only act as a proinflammatory cytokine but has at the same time the potential to reduce mucosal damage by preventing IEC apoptosis.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. florian.obermeier@klinik.uni-regensburg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Martin
authors.initials: M
authors.lastname: Hausmann
authors.forename: Silvia
authors.initials: S
authors.lastname: Kellermeier
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiessling
authors.forename: Ulrike G
authors.initials: UG
authors.lastname: Strauch
authors.forename: Erwin
authors.initials: E
authors.lastname: Duitman
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bock
authors.forename: Nadja
authors.initials: N
authors.lastname: Dunger
authors.forename: Michael
authors.initials: M
authors.lastname: Stoeck
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053148:Caspase 3