Cathepsin D is up-regulated in inflammatory bowel disease macrophages

Abstract

SUMMARYDown-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.

Quantitative Proteomics Analysis Reveals That Proteins Differentially Expressed in Chronic Pancreatitis Are Also Frequently Involved in Pancreatic Cancer

“…In breast cancer, cathepsin D is overexpressed from 2-to 50-fold compared with its concentration in other cell types such as fibroblasts or normal mammary glands (15). Up-regulated cathepsin D has also been detected in the inflammatory setting (16). The role of cathepsin D may make it a possible biomarker for diagnosis and prognosis of some cancers; however, the data in this study suggest that it is also up-regulated in chronic pancreatitis, limiting its use as biomarker for pancreatic cancer.…”

Immunohistochemical Study of Cathepsin D in the Spinal Cords of Rats with Clip Compression Injury

“…Moreover, the cellular infiltration and proliferation of macrophages and gliosis have been reported to occur at the injury site in rat spinal cords with a clip compression injury [8]. Cathepsin D expression increases in the macrophages observed in many inflammatory diseases, including inflammatory bowel disease [6], testicular ischemia/reperfusion injury [7] and chronic obstructive pulmonary disease [4]. In rat spinal cords with autoimmune inflammation, cathepsin D is expressed in the infiltrating macrophages [11].…”

Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

“…Although it has been known that normal intestinal macrophages show low proinflammatory activity, it has been shown that in intestinal diseases, particularly in CD, their profile differs considerably [13]. Indeed, these cells showed increased expression of co-stimulatory receptors, Toll-like receptors and inflammatory cytokines [18,19].…”

“…Peripheral blood monocytes have been divided into three distinct subsets according to CD14 and CD16 marker expression [18,20,21] + monocyte subsets, particularly the intermediate subset, have been associated with inflammatory functions [20] and are known to be the major producers of inflammatory cytokines such as TNF and interleukin (IL)-1β [22,23]. It was reported that, in CD patients with active disease, CD16…”