Menzel, K. and Hausmann, M. and Obermeier, F. and Schreiter, K. and Dunger, N. and Bataille, F. and Falk, W. and Schölmerich, J. and Herfarth, H. and Rogler, Gerhard (2006) Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 146 (1). pp. 169-180. ISSN 0009-9104, 1365-2249
Full text not available from this repository. (Request a copy)Abstract
The cathepsins D (CTSD), B (CTSB) and L (CTSL) are important for the intracellular degradation of proteins. Increased cathepsin expression is associated with inflammatory diseases. We have shown previously an induction of CTSD expression in intestinal macrophages (IMAC) in inflamed mucosa of patients with inflammatory bowel disease (IBD). Here we investigated the regulation of CTSB and CTSL in IMAC during IBD and effects of CTSD and CTSB/CTSL inhibition in vivo. Human IMAC were isolated from normal and inflamed mucosa. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for CTSB and CTSL mRNA. Immunostaining was used to confirm PCR results. Cathepsin inhibition was investigated in the dextran-sulphate-sodium (DSS) colitis model in mice with application of pepstatin A (CTSD inhibitor), CA-074 (CTSB inhibitor) and Z-Phe-Tyr-aldehyde (CTSL inhibitor). CTSL mRNA was significantly up-regulated in IMAC isolated from IBD mucosa. Up-regulated protein expression was found mainly in areas of mucosal damage by immunostaining. Inhibition of CTSD in mouse DSS colitis was followed by an amelioration of the disease. Inhibitor-treated mice showed a significant lower histological score (HS) and less colon reduction in comparison to controls. Similarly, simultaneous inhibition of CTSB/CTSL was followed by a significant amelioration of colitis. Expression of tissue-degrading cathepsins is increased in IMAC in IBD. Inhibition of CTSD as well as CTSB/CTSL is followed by an amelioration of experimental colitis. The prevention of mucosal damage by cathepsin inhibition could represent a new approach for the therapy of IBD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COSTIMULATORY MOLECULES; INTESTINAL MACROPHAGES; COLORECTAL CARCINOMAS; ANTIGEN PRESENTATION; CELLS; EXPRESSION; CANCER; PROTEINASES; PROTEOLYSIS; CYTOKINES; cathepsin B; cathepsin D; cathepsin L; DSS colitis; inflammatory bowel disease; inhibition; macrophages |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jan 2021 06:59 |
| Last Modified: | 25 Jan 2021 06:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33909 |
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