Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment

英夫利昔单抗 抗菌肽 炎症性肠病 医学 潘尼斯电池 克罗恩病 溃疡性结肠炎 炎症 免疫学 微阵列 基因表达 结肠炎 肠粘膜 内科学 胃肠病学 疾病 生物 抗菌剂 基因 微生物学 小肠 生物化学
作者
Ingrid Arijs,Gert De Hertogh,Katleen Lemaire,Roel Quintens,Leentje Van Lommel,Kristel Van Steen,Peter Leemans,Isabelle Cleynen,Gert Van Assche,Séverine Vermeire,Karel Geboes,Frans Schuit,Paul Rutgeerts
出处
期刊:PLOS ONE [Public Library of Science]
卷期号:4 (11): e7984-e7984 被引量:263
标识
DOI:10.1371/journal.pone.0007984
摘要

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.

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