title: Altered expression of IL36γ and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung's disease.
abstract: OBJECTIVE
  Hirschsprung's disease associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function and abnormal microbiota are implicated in the pathogenesis of HAEC. IL-36γ, a member of the IL-1 superfamily, is involved in host defense and contributes to proinflammatory responses and development of inflammatory diseases. The IL36 receptor (IL1RL2) is an important mediator molecule in the inflammatory response. Animal data suggests that IL1RL2 is involved in mucosal healing. We designed this study to investigate the hypothesis that the IL-36γ axis is altered in HSCR.
  
  
  METHODS
  We investigated IL-36γ and IL1RL2 expression in ganglionic and aganglionic bowel of HSCR patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed.
  
  
  RESULTS
  qPCR and Western blot analysis revealed that IL-36γ is strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. ILR1L2 expression was significantly decreased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of IL36γ in the colonic epithelium of patients with HSCR compared to controls. IL1RL2 was localized in the colonic epithelium and showed a markedly decreased expression in all HSCR specimens.
  
  
  CONCLUSIONS
  To our knowledge, we report for the first time the expression of IL36γ and ILRL2 in the colon of patients with HSCR. The increased expression of IL36γ and the markedly decreased expression of IL1RL2 in the aganglionic and ganglionic bowel in HSCR may result in an increased inflammatory response and altered mucosal response healing leading to the susceptibility to develop HAEC.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Christian
authors.initials: C
authors.lastname: Tomuschat
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: O'Donnell
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. prem.puri@ncrc.ie.|School of Medicine and Medical Science and Conway Institute of Biomedical Research, University College Dublin, Dublin, Ireland. prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism
chemical_list: C508589:IL36G protein, human; D007375:Interleukin-1; D018123:Receptors, Interleukin; C571244:interleukin-36 receptor, human
keywords: Hirschsprung’s associated enterocolitis (HAEC); Hirschsprung’s disease; IL1RL2; IL36γ; Inflammatory bowel disease