Natalia Fabisiak1,2, Adam Fabisiak1,3, Anna Chmielowiec-Korzeniowska4, Leszek Tymczyna4, Wojciech Kamysz5, Radzisław Kordek6, Marta Bauer5, Elżbieta Kamysz7, Jakub Fichna8. 1. Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland. 2. Department of Gastroenterology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. 3. Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. 4. Department of Animal Hygiene and Environment, University of Agriculture in Lublin, Lublin, Poland. 5. Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland. 6. Department of Pathology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. 7. Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland. 8. Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland. jakub.fichna@umed.lodz.pl.
Abstract
INTRODUCTION: Inflammatory bowel diseases (IBD) are a group of chronic gastrointestinal tract disorders with complex etiology, with intestinal dysbiosis as the most prominent factor. In this study, we assessed the anti-inflammatory and antibacterial actions of the human cathelicidin LL-37 and its shortest active fragment, KR-12 in the mouse models of colitis. MATERIALS AND METHODS: Mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and dextran sulfate sodium (DSS) were used in the study. The extent of inflammation was evaluated based on the macro- and microscopic scores, quantification of myeloperoxidase (MPO) activity and microbiological analysis of stool samples. RESULTS: A preliminary study with LL-37 and KR-12 (1 mg/kg, ip, twice daily) showed a decrease in macroscopic and ulcer scores in the acute TNBS-induced model of colitis. We observed that KR-12 (5 mg/kg, ip, twice daily) reduced microscopic and ulcer scores in the semi-chronic and chronic TNBS-induced models of colitis compared with inflamed mice. Furthermore, qualitative and quantitative changes in colonic microbiota were observed: KR-12 (5 mg/kg, ip, twice daily) decreased the overall number of bacteria, Escherichia coli and coli group bacteria. In the semi-chronic DSS-induced model, KR-12 attenuated intestinal inflammation as demonstrated by a reduction in macroscopic score and colon damage score and MPO activity. CONCLUSIONS: We demonstrated that KR-12 alleviates inflammation in four different mouse models of colitis what suggests KR-12 and cathelicidins as a whole are worth being considered as a potential therapeutic option in the treatment of IBD.
INTRODUCTION:Inflammatory bowel diseases (IBD) are a group of chronic gastrointestinal tract disorders with complex etiology, with intestinal dysbiosis as the most prominent factor. In this study, we assessed the anti-inflammatory and antibacterial actions of the human cathelicidin LL-37 and its shortest active fragment, KR-12 in the mouse models of colitis. MATERIALS AND METHODS:Mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and dextran sulfate sodium (DSS) were used in the study. The extent of inflammation was evaluated based on the macro- and microscopic scores, quantification of myeloperoxidase (MPO) activity and microbiological analysis of stool samples. RESULTS: A preliminary study with LL-37 and KR-12 (1 mg/kg, ip, twice daily) showed a decrease in macroscopic and ulcer scores in the acute TNBS-induced model of colitis. We observed that KR-12 (5 mg/kg, ip, twice daily) reduced microscopic and ulcer scores in the semi-chronic and chronic TNBS-induced models of colitis compared with inflamed mice. Furthermore, qualitative and quantitative changes in colonic microbiota were observed: KR-12 (5 mg/kg, ip, twice daily) decreased the overall number of bacteria, Escherichia coli and coli group bacteria. In the semi-chronic DSS-induced model, KR-12attenuated intestinal inflammation as demonstrated by a reduction in macroscopic score and colon damage score and MPO activity. CONCLUSIONS: We demonstrated that KR-12 alleviates inflammation in four different mouse models of colitis what suggests KR-12 and cathelicidins as a whole are worth being considered as a potential therapeutic option in the treatment of IBD.
Authors: Marta Sobczak; Adam Fabisiak; Natalia Murawska; Ewelina Wesołowska; Paulina Wierzbicka; Marcin Wlazłowski; Marta Wójcikowska; Hubert Zatorski; Marta Zwolińska; Jakub Fichna Journal: Pharmacol Rep Date: 2014-04-29 Impact factor: 3.024
Authors: Hon Wai Koon; David Q Shih; Jeremy Chen; Kyriaki Bakirtzi; Tressia C Hing; Ivy Law; Samantha Ho; Ryan Ichikawa; Dezheng Zhao; Hua Xu; Richard Gallo; Paul Dempsey; Genhong Cheng; Stephan R Targan; Charalabos Pothoulakis Journal: Gastroenterology Date: 2011-07-14 Impact factor: 22.682
Authors: John Gubatan; Derek R Holman; Christopher J Puntasecca; Danielle Polevoi; Samuel Js Rubin; Stephan Rogalla Journal: World J Gastroenterol Date: 2021-11-21 Impact factor: 5.742