Jan Wehkamp1, Michael Schmid, Eduard F Stange. 1. Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.
Abstract
PURPOSE OF REVIEW: Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed. RECENT FINDINGS: Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as well as the cathelicidin LL37. The attenuated induction of beta defensins is linked to fewer gene copy numbers in this locus, which is associated with colonic but not ileal Crohn's disease. In contrast, ileal Crohn's disease patients are characterized by a reduced antibacterial activity and a specific reduction of ileal Paneth cell defensins. This decrease is independent of the grade of histological inflammation and cannot be found in inflammation controls. Thus, some of these defects can be explained either by direct or indirect genetic mechanisms and appear to be primary. SUMMARY: Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.
PURPOSE OF REVIEW: Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed. RECENT FINDINGS: Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as well as the cathelicidin LL37. The attenuated induction of beta defensins is linked to fewer gene copy numbers in this locus, which is associated with colonic but not ileal Crohn's disease. In contrast, ileal Crohn's diseasepatients are characterized by a reduced antibacterial activity and a specific reduction of ileal Paneth cell defensins. This decrease is independent of the grade of histological inflammation and cannot be found in inflammation controls. Thus, some of these defects can be explained either by direct or indirect genetic mechanisms and appear to be primary. SUMMARY: Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.
Authors: Roni Nowarski; Ruaidhrí Jackson; Nicola Gagliani; Marcel R de Zoete; Noah W Palm; Will Bailis; Jun Siong Low; Christian C D Harman; Morven Graham; Eran Elinav; Richard A Flavell Journal: Cell Date: 2015-12-03 Impact factor: 41.582
Authors: Harry Sokol; Nadia Vasquez; Nadia Hoyeau-Idrissi; Philippe Seksik; Laurent Beaugerie; Anne Lavergne-Slove; Philippe Pochart; Philippe Marteau Journal: World J Gastroenterol Date: 2010-02-07 Impact factor: 5.742
Authors: Michael Gersemann; Jan Wehkamp; Klaus Fellermann; Eduard Friedrich Stange Journal: World J Gastroenterol Date: 2008-09-28 Impact factor: 5.742