Cathepsin D is up-regulated in inflammatory bowel disease macrophages

Hausmann, Martin and Obermeier, F. and Schreiter, K. and Spottl, T. and Falk, W. and Schoelmerich, Juergen and Herfarth, H. and Saftig, P. and Rogler, G. (2004) Cathepsin D is up-regulated in inflammatory bowel disease macrophages. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 136 (1). pp. 157-167. ISSN 0009-9104, 1365-2249

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Abstract

Down-regulation of receptors involved in the recognition or transmission of inflammatory signals and a reduced responsiveness support the concept that macrophages are 'desensitized' during their differentiation in the intestinal mucosa. During inflammatory bowel disease (IBD) intestinal macrophages (IMACs) change to a reactive or 'aggressive' type. After having established a method of isolation and purification of IMACs, message for cathepsin D was one of the mRNAs we found to be up-regulated in a subtractive hybridization of Crohn's disease (CD) macrophages versus IMACs from control mucosa. The expression of cathepsin D in intestinal mucosa was analysed by immunohistochemistry in biopsies from IBD and control patients and in a mouse model of dextran sulphate sodium (DSS)-induced acute and chronic colitis. IMACs were isolated and purified from normal and inflamed mucosa by immunomagnetic beads armed with a CD33 antibody. RT-PCR was performed for cathepsin D mRNA. Results were confirmed by Northern blot and flow cytometrical analysis. Immunohistochemistry revealed a significant increase in the cathepsin D protein expression in inflamed intestinal mucosa from IBD patients compared to non-inflamed mucosa. No cathepsin D polymerase chain reaction (PCR) product could be obtained with mRNA from CD33-positive IMACs from normal mucosa. Reverse transcription (RT)-PCR showed an induction of mRNA for cathepsin D in purified IMACs from IBD patients. Northern blot and flow cytometry analysis confirmed these results. Cathepsin D protein was also found in intestinal mucosa in acute and chronic DSS-colitis but was absent in normal mucosa. This study shows that expression of cathepsin D is induced in inflammation-associated IMACs. The presence of cathepsin D might contribute to the mucosal damage in IBD.

Item Type: Article
Uncontrolled Keywords: ANTIGEN PRESENTATION; BREAST-CANCER; EXTRACELLULAR-MATRIX; COSTIMULATORY MOLECULES; INTESTINAL MACROPHAGES; BONE-RESORPTION; CELLS; EXPRESSION; PROTEASES; MUCOSA; cathepsin D; inflammatory bowel disease; macrophages
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Jul 2021 05:04
Last Modified: 26 Jul 2021 05:04
URI: https://pred.uni-regensburg.de/id/eprint/37771

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