Role of cannabinoid receptors and RAGE in inflammatory bowel disease
Sebastian Stintzing1*, Till Th. Wissniowski2*, Christina Lohwasser2, Beate Alinger3, Daniel Neureiter3 and Matthias Ocker2,4
1Department of Medicine III, University Hospital Grosshadern, Munich, Germany, 2Department of Medicine 1, University Hospital Erlangen, Germany, 3Institute of Pathology, Landeskliniken Salzburg, Paracelsus Medical University, Austria and 4Institute for Surgical Research, Philipps University Marburg, Germany
*Both authors contributed equally to the work, M.O. and D.N. are considered equal senior authors.
Offprint requests to: Sebastian Stintzing, MD, Department of Medicine III, University Hospital Grosshadern, University of Munich, Marchinoninistrasse 15, 81377 Munich, Germany. e-mail: sebastian.stintzing@med.uni-muenchen.de
Summary. Background: The endocanabinoid system is involved in many inflammatory diseases, such as Crohn’s disease (CD) and ulcerative colitis (UC). The distribution and expression of cannabinoid receptors 1 (CNR1) and 2 (CNR2) in combination with inflammatory cytokines and RAGE (receptor of advanced glycation end products), which is also overactive in these diseases, in dependency of the extent of inflammation and alteration of the colon barrier is still unclear and needs to be elucidated. Material and Methods: 10 specimens of CD patients who underwent colectomy and 14 colectomy specimens of patients suffering from UC were investigated histologically for inflammatory infiltrate, extent of fibrosis and for disturbance of the intestinal barrier. Immunohistochemistry was carried out to examine the distribution and localization of CNR1, CNR2 and RAGE. Additionally, qRT-PCR was performed to study the expression of CNR1, CNR2, RAGE and inflammatory cytokines (TNFα, TGFß, CTGF, IL12, IFNγ). 35 morphological and histological normal specimens of colectomy cases served as controls. Results: The expression level of CNR2 did not differ between the control group and the group of patients with IBD, while CNR1 displayed a significant up regulation, especially in cases of CD. A differential association between the expression of CNR1/CNR2 and RAGE with morphological changes and expression of molecular markers of inflammation could be established. Conclusion: We showed that cannabinoid receptors are expressed differentially in inflammatory bowel disease and that the expression seems to be influenced by the underlying disease and by localized inflammation. Histol Histopathol 26, 735-745 (2011)
Key words: CNR1, CNR2, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis
DOI: 10.14670/HH-26.735