Expression of catalytic proteasome subunits in the gut of patients with Crohn's disease.
OBJECTIVE
Activation of the transcription factor NF-kappaB by proteasomes and subsequent nuclear translocation of cytoplasmatic complexes play a crucial role in the intestinal inflammation. Proteasomes have a pivotal function in NF-kappaB activation by mediating degradation of inhibitory IkappaB proteins and processing of NF-kappaB precursor proteins. This study aims to analyze the expression of the human proteasome subunits in colonic tissue of patients with Crohn's disease.


METHODS
Thirteen patients with Crohn's disease and 12 control patients were studied. The expression of immunoproteasomes and constitutive proteasomes was examined by Western blot analysis, immunoflourescence and quantitative real-time PCR. For real-time PCR, AK2C was used as housekeeping gene.


RESULTS
The results indicate the influence of the intestinal inflammation on the expression of the proteasomes in Crohn's disease. Proteasomes from inflamed intestine of patients with Crohn's disease showed significantly increased expression of immunosubunits on both protein and mRNA levels. Especially, the replacement of the constitutive proteasome subunit beta1 by inducible immunosubunit beta1i was observed in patients with active Crohn's disease. In contrast, relatively low abundance of immunoproteasomes was found in control tissue.


CONCLUSIONS
Our data demonstrate that in contrast to normal colonic tissue, the expression of immunoproteasomes was evidently increased in the inflamed colonic mucosa of patients with Crohn's disease. Thus, the chronic intestinal inflammation process in Crohn's disease leads to significant alterations of proteasome subsets.
Visekruna
Alexander
A
Department of Surgery I, Charité-Medical School, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. alexander.visekruna@charite.de
Slavova
Nadia
N
Dullat
Sonja
S
Gröne
Jörn
J
Kroesen
Anton-Josef
AJ
Ritz
Jörg-Peter
JP
Buhr
Heinz-Johannes
HJ
Steinhoff
Ulrich
U
D016022:Case-Control Studies; D020134:Catalytic Domain / Q000235:genetics*; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D041981:Gastrointestinal Tract / Q000201:enzymology* / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex