Mucosal gene expression of antimicrobial peptides in inflammatory bowel disease before and after first infliximab treatment

• Published in: PloS one Vol. 4; no. 11; p. e7984
• Main Authors: Arijs, Ingrid, De Hertogh, Gert, Lemaire, Katleen, Quintens, Roel, Van Lommel, Leentje, Van Steen, Kristel, Leemans, Peter, Cleynen, Isabelle, Van Assche, Gert, Vermeire, Séverine, Geboes, Karel, Schuit, Frans, Rutgeerts, Paul
• Format: Journal Article Web Resource
• Language: English
• Published: United States Public Library of Science 24.11.2009; Public Library of Science (PLoS)
• Subjects: Adult; alpha-defensin expression; Analysis; Anti-Inflammatory Agents - pharmacology; Antibiotics; Antibodies, Monoclonal - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Bayesian analysis; Bioinformatics; Biology; Biopsy; Chemokines; Colon; Computer engineering; Computer science; Crohn Disease - metabolism; Crohn's Disease; Data processing; Defensins; Digestive tract; DNA microarrays; Electrical engineering; Epithelial cells; Female; Gastroenterology; Gastroenterology & hepatology; Gastroenterology and Hepatology/Inflammatory Bowel Disease; Gastroentérologie & hépatologie; Gastrointestinal diseases; Gene expression; Gene Expression Regulation; Genes; Genetics and Genomics/Gene Expression; Genetics and Genomics/Pharmacogenomics; Genomes; Human health sciences; Humans; Hypotheses; ileal crohns-disease; Ileum; Immune system; Immunohistochemistry; Immunohistochemistry - methods; Immunotherapy; induction; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - microbiology; Infliximab; Intestinal Mucosa - metabolism; Intestine; Male; Mathematical models; Medical research; Medical treatment; mice; Microorganisms; Middle Aged; Monoclonal antibodies; Morphology; Mucosa; Mucous Membrane - metabolism; Neuropeptides; Nutrition research; Oligonucleotide Array Sequence Analysis; Patients; Peptides; Peptides - metabolism; Polymerase chain reaction; Proteins; Rodents; Sciences de la santé humaine; system; Therapy; Tumor necrosis factor-a; Tumor necrosis factor-α; ulcerative-colitis; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007984

Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD. Mucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4-6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage. Our study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms.