Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases.
BACKGROUND
Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease.


METHODS
Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production.


RESULTS
Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells.


CONCLUSIONS
In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.
Schauber
Jürgen
J
Department of Medicine II, Division of Gastroenterology cInstitute of Pathology, University of Würzburg, Germany. jschauber@ucsd.edu
Rieger
Daniel
D
Weiler
Frank
F
Wehkamp
Jan
J
Eck
Matthias
M
Fellermann
Klaus
K
Scheppach
Wolfgang
W
Gallo
Richard L
RL
Stange
Eduard F
EF
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins