title: Infliximab therapy reverses the increase of allograft inflammatory factor-1 in serum and colonic mucosa of rats with inflammatory bowel disease.
abstract: OBJECTIVE
  Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing.
  
  
  METHODS
  Healthy rats and rats which were subjected to experimental colitis induced by dextran sulfate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBD patients. Colon mucosal integrity by periodic acid Schiff (PAS) staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, β-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats while serum and colon AIF-1 levels were determined in IBD patients.
  
  
  RESULTS
  In rats with colitis, IFX reestablished the epithelial barrier integrity, recovered mucus production and decreased colon inflammation, as verified by reduced serum and colon AIF-1 levels; colon and serum AIF-1 levels were also lower in inactive IBD patients compare to active ones. P38 activation after IFX treatment tended to induce differentiation/proliferation of epithelial cells along the colonic crypt-villous axis.
  
  
  CONCLUSIONS
  These findings support AIF-1 as a new biomarker of mucosal healing in experimental colitis and suggest that p38 activation is involved in the mucosal healing intracellular mechanism induced by IFX treatment.
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: Irene D
authors: ID
authors: Román
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: David
authors: D
authors: Cano-Martínez
authors: b Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá de Henares , Spain.
authors: María Val T
authors: MV
authors: Lobo
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: María Dolores
authors: MD
authors: Fernández-Moreno
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: Borja
authors: B
authors: Hernández-Breijo
authors: c Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS) , Madrid , Spain.
authors: Silvia
authors: S
authors: Sacristán
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: Patricia
authors: P
authors: Sanmartín-Salinas
authors: d Department of Medicine , University of Alcalá , Alcalá de Henares , Spain.
authors: Jorge
authors: J
authors: Monserrat
authors: e Gastroenterology Unit , Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) , Madrid , Spain.
authors: Javier P
authors: JP
authors: Gisbert
authors: a Department of Systems Biology , Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Alcalá , Alcalá de Henares , Spain.
authors: Luis G
authors: LG
authors: Guijarro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D004268:DNA-Binding Proteins / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy*; D000069285:Infliximab / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects*; D008840:Microfilament Proteins / Q000097:blood* / Q000187:drug effects; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C112986:AIF1 protein, human; C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D000069285:Infliximab; D048051:p38 Mitogen-Activated Protein Kinases
keywords: IBD; dextran sulfate sodium; mucin; p-p38