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Abstracts (complete list) - Wissenschaft Online

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Ulrich Steinhoff, Alexander Visekruna, Anjo Kroesen<br />

The proteasome controls NF-κB-mediated inflammation in IBD<br />

patients<br />

Proteasomes are the central proteolytic machinery of cells involved in degradation of<br />

proteins and generation of MHC class I epitopes. Additionally they play a central role in<br />

regulation of inflammatory processes mediated by NF-κB. We analyzed the structure<br />

and function of 20S proteasomes in normal and inflamed intestinal tissues from Crohn’s<br />

disease (CD)and ulcerative colitis (UC) patients.<br />

Our results show tissue-specific differences in proteasome composition as previously<br />

reported in mice.<br />

However, we found marked differences in proteasome composition between CD and UC<br />

patients. Inflammation affected the proteasome composition only in CD patients with<br />

strong expression of immunosubunits in the inflamed tissues.<br />

Immunoproteasomes isolated from CD patients degraded IκBα and processed p105<br />

much faster than constitutive proteasomes from UC patients. Immunohistochemical<br />

analysis confirmed that the amount of activated NF-κB correlated with the expression of<br />

immunoprotesasomes.<br />

This demonstrates that the mechanism of inflammation differs between UC and CD<br />

patients and that proteasomes are crucially involved in Th1-mediated inflammation.

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