Immunosuppressive circular plant peptides

Abstract

Event Abstract Back to Event Immunosuppressive circular plant peptides Kathrin Thell1, Roland Hellinger1, Emine Sahin1, Carsten Gründemann2, Gernot Schabbauer1* and Christian W. Gruber1* 1 Medical University of Vienna, Center for Physiology and Pharmacology, Austria 2 University Medical Center Freiburg, Center for Complementary Medicine, Germany Background: The immune system is constantly detecting and removing endogenous and exogenous threats, but sparing the organism's own cells and tissues. In case of a dysregulated immune system, like in autoimmunity, this homeostasis is destroyed. Cyclosporine A, a naturally-occurring circular depsipeptide, is routinely used in clinics as immunosuppressant, but provokes many and often severe side-effects. Recently we identified circular peptides from plants, which exhibit promising anti-proliferative effects towards T-cells. These so-called cyclotides are composed of about 30 amino acids with a head-to-tail cyclized backbone. Their six conserved cysteines that are arranged in a typical cyclic cystine-knot motif, confers them with resistance to enzymatic, chemical or thermal degradation, making them attractive pharmaceutical tools. Aim: The aim of this study is to investigate the immunosuppressive properties and mechanism of native and synthetic cyclotides in vitro and in vivo, and compare their mode-of-action to other immunosuppressive drugs such as cyclosporine A. Methods & Results: We were able to demonstrate their anti-proliferative characteristics towards human activated primary lymphocytes in vitro. This significant inhibitory effect was dose-dependent and no cytotoxicity was observed in the active concentration range. Furthermore an experimental autoimmune encephalomyelitis mouse model was used to test the therapeutic impact on lymphocyte proliferation in vivo. We could show significantly delayed and minor symptoms of disease in mice treated with cyclotides. Moreover the anti-proliferative effects could be confirmed in isolated restimulated mouse splenocytes in vitro. Conclusion: Cyclotides have great potential as peptide-based drugs and display promising immunosuppressive properties towards lymphocytes in vitro and in vivo. Acknowledgements We would like to thank A. Dohnal from Children's Cancer Research Institute Vienna for providing purified lymphocytes. Work on immunosuppressive peptides in the laboratory of C.W.G is funded by the Austrian Science Fund (FWF-P24743). References Gründemann C, Koehbach J, Huber R and Gruber CW. Do plant cyclotides have potential as immunosuppressant peptides? J Nat Prod (2012) 75: 167-174. Craik DJ, Swedberg JE, Mylne JS and Cemazar M. Cyclotides as a basis for drug design. Expert Opin Drug Discov (2012) 7: 179-194. Keywords: circular plant peptides, Cyclotides, kalata B1, Immunosuppression, Cyclosporine A, Experimental autoimmune encephalomyelitis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Thell K, Hellinger R, Sahin E, Gründemann C, Schabbauer G and Gruber CW (2013). Immunosuppressive circular plant peptides. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00362 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Gernot Schabbauer, Medical University of Vienna, Center for Physiology and Pharmacology, Vienna, Austria, gernot.schabbauer@meduniwien.ac.at Dr. Christian W Gruber, Medical University of Vienna, Center for Physiology and Pharmacology, Vienna, Austria, christian.gruber@meduniwien.ac.at Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kathrin Thell Roland Hellinger Emine Sahin Carsten Gründemann Gernot Schabbauer Christian W Gruber Google Kathrin Thell Roland Hellinger Emine Sahin Carsten Gründemann Gernot Schabbauer Christian W Gruber Google Scholar Kathrin Thell Roland Hellinger Emine Sahin Carsten Gründemann Gernot Schabbauer Christian W Gruber PubMed Kathrin Thell Roland Hellinger Emine Sahin Carsten Gründemann Gernot Schabbauer Christian W Gruber Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.