title: Increased Act1/IL-17R expression in 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 is implicated in the pathogenesis of HAEC. IL-17 is a proinflammatory cytokine that plays a crucial role in host defense against microbial organisms in the development of inflammatory diseases. Act1 is an essential adaptor molecule required for the IL-17-mediated inflammatory responses via interaction with IL-17 receptor (IL-17R). We designed this study to investigate the hypothesis that Act1/Il-17R expression is upregulated in HSCR.
  
  
  METHODS
  We investigated Act1 and IL17R expression in ganglionic andaganglionic bowel of HD patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed.
  
  
  RESULTS
  qPCR and Western blot analysis revealed that Act1 and IL17R are strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. Act1 and IL17R expression was significantly increased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of Act1 and IL17R in the colonic epithelium of patients with HSCR compared to controls.
  
  
  CONCLUSIONS
  To our knowledge, we report, for the first time, the expression of Act1 in the human colon. The increased expression of Act1 and Il-17 in the aganglionic and ganglionic bowel in HSCR may result in IL-17-mediated increased inflammatory response leading to the development of 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, 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: D048868:Adaptor Proteins, Signal Transducing; D015153:Blotting, Western; D005260:Female; D005455:Fluorescent Antibody Technique; D005724:Ganglia / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D020381:Interleukin-17 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D008297:Male; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020381:Interleukin-17; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
keywords: Act1; Hirschsprung’s disease; Hirschsprung’s-associated enterocolitis (HAEC); IL17R; Inflammatory bowel disease