title: Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation.
abstract: OBJECTIVE
  Infiltration of activated immune cells and increased cytokine production define the immunophenotype of gastrointestinal (GI) inflammation. In addition, intestinal inflammation is accompanied by alteration in the numbers of serotonin (5-hydroxytryptamine; 5-HT) synthesizing enterochromaffin (EC) cells and in 5-HT amount. It has been established that EC cells express interleukin (IL)-13 receptor, additionally IL-13 has been implicated in the pathogenesis of ulcerative colitis. In this study, we investigated the role of IL-13 mediated 5-HT signaling in pathogenesis of colitis.
  
  
  METHODS
  Colitis was induced in IL-13 deficient (IL-13-/-) and wild-type (WT) mice with dextran sulfate sodium (DSS) and dinitrobenzene sulfonic acid (DNBS), as well as in IL-13-/- mice given recombinant mouse IL-13 (rmIL-13) and 5-hydroxytryptamine (5-HTP), the direct precursor of 5-HT.
  Elevated colonic IL-13 levels were observed in WT mice receiving DSS in comparison to control. IL-13-/- mice administered DSS exhibited significantly reduced severity of colitis compared to WT mice as reflected by macroscopic and histological damage assessments. Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT. The reduced severity of colitis observed in IL-13-/- mice was also accompanied by down-regulation of EC cell numbers and colonic 5-HT content. In addition, increasing colonic 5-HT content by administration of rmIL-13 or 5-HTP exacerbated severity of DSS colitis in IL-13-/- mice. IL-13-/- mice also exhibited reduced severity of DNBS-induced colitis. These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation. This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.
authors.affiliation: Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada ; Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Md Sharif
authors.initials: MS
authors.lastname: Shajib
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Ivana
authors.initials: I
authors.lastname: Sunjic
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Denou
authors.forename: Matthew
authors.initials: M
authors.lastname: Collins
authors.forename: Judah A
authors.initials: JA
authors.lastname: Denburg
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000633:toxicity; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004703:Endocrine System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012701:Serotonin / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001557:Benzenesulfonates; D018793:Interleukin-13; C007488:dinitrobenzenesulfonic acid; D012701:Serotonin; D016264:Dextran Sulfate