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


RESULTS
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.


CONCLUSIONS
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.
Arijs
Ingrid
I
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
De Hertogh
Gert
G
Lemaire
Katleen
K
Quintens
Roel
R
Van Lommel
Leentje
L
Van Steen
Kristel
K
Leemans
Peter
P
Cleynen
Isabelle
I
Van Assche
Gert
G
Vermeire
Séverine
S
Geboes
Karel
K
Schuit
Frans
F
Rutgeerts
Paul
P
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D003424:Crohn Disease / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000382:microbiology*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D000069285:Infliximab