Intestinal tissue kallikrein–kallistatin profile in inflammatory bowel disease $ Antoni Stadnicki a, * , Urszula Mazurek b , Danuta Plewka c , Tadeusz Wilczok b a Department of Internal Medicine, Medical University of Silesia, St. Barbara’s Hospital, Medyk Sq. 1, 41-200 Sosnowiec, Katowice, Poland b Department of Molecular Biology, Biochemistry and Biopharmacy, Medical University of Silesia, Katowice, Poland c Department of Histology and Embryology, Medical University of Silesia, Katowice, Poland Received 19 February 2003; received in revised form 19 February 2003; accepted 20 February 2003 Abstract The profile of tissue kallikrein (TK) and its inhibitor, kallistatin was evaluated in patients with active ulcerative colitis (UC) and Crohn’s disease (CD). Tissue kallikrein is mainly localized to goblet cells and kallistatin to epithelial cells of human intestine. Intestinal tissue kallikrein (ITK) and kallistatin are significantly decreased in inflamed intestine compared to noninflammatory controls. TK mRNA as well as kallistatin mRNA is significantly decreased in intestinal biopsy samples from UC-active patients compared with controls. The difference in distribution and levels of ITK and kallistatin in protein and mRNA in patients with inflammatory bowel disease (IBD) compared to controls suggest a role in inflammatory state. D 2003 Elsevier Science B.V. All rights reserved. Keywords: Ulcerative colitis; Tissue kallikrein; Kallistatin; Bradykinin 1. Introduction Inflammatory bowel disease (IBD), namely Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, spontaneously relapsing disorders. The causes of the diseases are unknown. They display genetic and envi- ronmental components, and appear to be mediated by activation of immune system cells and plasma proteo- lytic cascades [1]. The kallikrein – kinin system is a part of the humoral defense system that participates in the inflammatory response. The kallikreins are serine pro- teases that are divided into two main types, plasma kallikrein (PK) and tissue kallikrein (TK). A single gene codes for PK, which is synthesized in the liver, whereas tissue kallikrein is a member of a multigene family that shows different patterns of tissue specific gene expression [2]. Both kallikreins are potent kinin— generating enzymes by cleaving of kininogens, their physiological substrates. Bradykinin (BK) is released by PK or TK from of either or both of the plasma kininogens. Plasma kallikrein cleaves bradykinin from its preferred sub- strate, high molecular weight kininogen (HMWK). Tissue (glandular) kallikrein releases lysyl –BK (itself a potent kinin) from HMWK that is then converted to bradykinin by plasma aminopeptidases [3]. In a rat 1567-5769/03/$ - see front matter D 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1567-5769(03)00054-7 $ This paper is part of the Proceedings of the 16th International Conference on the Kallikrein-Kinin System (Kinin 2002) which was held in Charleston, SC, May 26 – 31, 2002 (see International Immunopharmacology Volume 2/13–14). * Corresponding author. Fax: +48-32-3682111. E-mail address: astadnic@wp.pl (A. Stadnicki). www.elsevier.com/locate/intimp International Immunopharmacology 3 (2003) 939 – 944