Enhanced intestinal expression of the proteasome subunit low molecular mass polypeptide 2 in patients with inflammatory bowel disease.
OBJECTIVE
Low molecular mass polypeptide 2 is an inducible immunoproteasome subunit. The expression of low molecular mass polypeptide 2 has not been examined in the intestine of patients with inflammatory bowel disease. This study was designed to determine whether the intestinal expression of low molecular mass polypeptide 2 was enhanced in a group of patients with inflammatory bowel disease compared with a group of control patients without inflammatory bowel disease. Moreover, we examined the association between low molecular mass polypeptide 2 expression and histologic pathology in these patients.


METHODS
Twenty-one patients participated in the study. These included six control subjects without inflammatory bowel disease, eight patients with ulcerative colitis, and seven patients with Crohn's disease. Intestinal low molecular mass polypeptide 2 expression was evaluated by immunohistochemistry, as well as by Western blot. Histology scores (0-40 severity scale) were determined on the same sections of intestine as those used for low molecular mass polypeptide 2 histochemistry.


RESULTS
By immunohistochemistry, low molecular mass polypeptide 2 expression was significantly enhanced (P < 0.05 vs. control subjects) throughout visibly diseased areas of colon, rectum, and ileum from patients with inflammatory bowel disease. Low molecular mass polypeptide 2 expression also was increased in macroscopically normal intestine from patients with inflammatory bowel disease compared with normal tissue from control subjects. There was a significant correlation (P < 0.0001) between low molecular mass polypeptide 2 expression and histologic pathology in our patients. Western blot results confirmed that low molecular mass polypeptide 2 expression was enhanced in patients with ulcerative colitis (3.1-fold) and in patients with Crohn's disease (3.5-fold).


CONCLUSIONS
Intestinal low molecular mass polypeptide 2 expression is significantly increased in inflammatory bowel disease. The association between intestinal low molecular mass polypeptide 2 expression and histologic pathology suggests that this proteasome subunit plays a role in the pathogenesis of inflammatory bowel disease.
Fitzpatrick
Leo R
LR
Department of Surgery, Section of Colon and Rectal Surgery, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA. lfitzpatrick@psu.edu
Small
Jeffrey S
JS
Poritz
Lisa S
LS
McKenna
Kevin J
KJ
Koltun
Walter A
WA
D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D016015:Logistic Models; D008297:Male
C071313:LMP-2 protein; D003546:Cysteine Endopeptidases