title: IL-13 orchestrates resolution of chronic intestinal inflammation via phosphorylation of glycogen synthase kinase-3β.
abstract: Spontaneous amelioration of inflammation (often accompanied by fibrosis) is a well-known, but poorly understood, outcome of many chronic inflammatory processes. We studied this phenomenon in a chronic trinitrobenzene sulfonic acid-induced colitis model, an experimental colitis in mice that we showed to ultimately undergo spontaneous resolution, despite continued trinitrobenzene sulfonic acid stimulation. Analysis of the mechanism of this resolution revealed that it was critically dependent on IL-13 activation of STAT6, followed by phosphorylation (inactivation) of glycogen synthase kinase-3β, at least in part via STAT6 induction of p38 MAPK. Such glycogen synthase kinase-3β inactivation causes changes in CREB and p65 DNA-binding activity that favors decreased proinflammatory IL-17 production and increased anti-inflammatory IL-10 production. Thus, in this case, IL-13 acts as a molecular switch that leads to resolution of inflammation.
authors.affiliation: Department of Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Fichtner-Feigl
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kesselring
authors.forename: Maria
authors.initials: M
authors.lastname: Martin
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kitani
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Brunner
authors.forename: Michael
authors.initials: M
authors.lastname: Haimerl
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D015398:Signal Transduction; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D014302:Trinitrobenzenesulfonic Acid; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3