title: Integrative Network-based Analysis of Colonic Detoxification Gene Expression in Ulcerative Colitis According to Smoking Status.
abstract: OBJECTIVE
  The effect of cigarette smoking [CS] is ambivalent since smoking improves ulcerative colitis [UC] while it worsens Crohn's disease [CD]. Although this clinical relationship between inflammatory bowel disease [IBD] and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes.
  
  
  METHODS
  A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers [n = 8] and non-smokers [n = 9] versus the non-affected colonic mucosa of UC patients [n = 19] was performed by quantitative real-time polymerase chain reaction [qRT PCR]. The detoxification gene expression profile was analysed in CD patients [n = 18], in smoking UC patients [n = 5], and in biopsies from non-smoking UC patients cultured or not with cigarette smoke extract [n = 8].
  
  
  RESULTS
  Of the 244 detoxification genes investigated, 65 were dysregulated in UC patients in comparison with healthy controls or CD patients. The expression of ≥ 45/65 genes was inversed by CS in biopsies of smoking UC patients in remission and in colonic explants of UC patients exposed to cigarette smoke extract. We devised a network-based data analysis approach for differentially assessing changes in genetic interactions, allowing identification of unexpected regulatory detoxification genes that may play a major role in the beneficial effect of smoking on UC.
  
  
  CONCLUSIONS
  Non-inflamed colonic mucosa in UC is characterised by a specifically altered detoxification gene network, which is partially restored by tobacco. These mucosal signatures could be useful for developing new therapeutic strategies and biomarkers of drug response in UC.
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Ding
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Ladeiro
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Université Paris 13, Sorbonne Paris Cité, Villetaneuse, France.
authors.forename: Ian
authors.initials: I
authors.lastname: Morilla
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Assistance Publique Hôpitaux de Paris, Service de gastroentérologie, MICI et assistance nutritive, Hôpital Beaujon, Clichy la Garenne, France.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.
authors.forename: Assiya
authors.initials: A
authors.lastname: Marah
authors.affiliation: Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Université Paris 13, Sorbonne Paris Cité, Villetaneuse, France.
authors.forename: Hatem
authors.initials: H
authors.lastname: Zaag
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Assistance Publique Hôpitaux de Paris, Service d'anatomopathologie, Hôpital Beaujon, Clichy la Garenne, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals-Hatem
authors.affiliation: INSERM U1157, UMR 7203, F-7502, Paris, France.|Assistance Publique Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Seksik
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Daniel
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.affiliation: Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Département d'Informatique, Equipe DATA, Ecole Normale Supérieure, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Wainrib
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.|Assistance Publique Hôpitaux de Paris, Service de gastroentérologie, MICI et assistance nutritive, Hôpital Beaujon, Clichy la Garenne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Tréton
authors.affiliation: INSERM, Research Centre of Inflammation BP 416, Paris, France.|Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|Laboratory of Excellence Labex INFLAMEX, Sorbonne-Paris- Cité, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Ogier-Denis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
keywords: Cigarette smoke; detoxification genes; inflammatory bowel diseases; network inference; ulcerative colitis