Title: Genistein derivatives down-modulates pro-inflammatory cytokines in activated J774A.1 cells and reverses clinical signs of experimental autoimmune encephalomyelitis
Abstract: Event Abstract Back to Event Genistein derivatives down-modulates pro-inflammatory cytokines in activated J774A.1 cells and reverses clinical signs of experimental autoimmune encephalomyelitis Sandra B. Castro1*, Celso O. Junior2, Caio Cesar Souza Alves1, Alyria T. Dias1, Maria A. Juliano3, Maria C. Castañon4, Mauro V. Almeida2, Henrique C. Teixeira1 and Ana Paula Ferreira1 1 Universidade Federal de Juiz de Fora, Parasitologia, Microbiologia e Imunologia, Brazil 2 Universidade Federal de Juiz de Fora, Quimica, Brazil 3 Universidade Federal de Sao Paulo, Biofisica, Brazil 4 Universidade Federal de Juiz de Fora, Morfologia, Brazil Genistein down modulate pro-inflammatory cytokine by inhibiting the NF-κB signaling pathway. Although genistein has some potential in clinical application, it has some disadvantages related to its chemical structure, such as rapid in vivo metabolism and a low concentration in serum after oral administration. In this report, the immunomodulatory effect of genistein derivatives on the production of pro-inflammatory cytokines by activated macrophages and their applications in EAE model were investigated. J774A.1 macrophages were incubated in the presence of genistein or genistein derivatives. Supernatants were collected for cytokine, NO and MTT assay. C57BL/6 mice were immunized with MOG35-55 and treated or not with genistein or genistein derivative. Mice were sacrificed on the 21st dpi and brains were removed for histological, cytokine production and cell markers analysis. In J774A.1 macrophages the genistein has inhibited both IL-12 and TNF-α, the lipophilic derivatives showed high capacity to inhibit IL-12 without altering TNF-α, indicating a more specific mechanism in the modulation of IL-12 and the glycosylated derivative AAP37A showed elevated inhibition of NO (100.0±0.5), IL-1β (100.0±12.9) and IL-6 (94.1±5.9). Treatment with O-tetradecanoyl-genistein derivative improved prognosis of EAE by reduction of inflammatory infiltrate, decrease of pro-inflammatory cytokines and reduction of cells producing IL-17 (0.6±0.03 vs. 3.5±0.6), and increasing of cells producing IL-10 (0.6±0.1 vs. 0.1±0.07) and expressing FOXP3 (1.4±0.2 vs. 0.3±0.1) and CTLA-4 (4.8±0.4 vs. 1.0±0.04) in the central nervous system. Thus, these derivatives showed potential to be used in the treatment of inflammatory diseases and deserve further investigations. Financial support: CNPq, CAPES, FAPEMIG. Keywords: Genistein, EAE/MS, IL-17, IL-10, derivatives Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Castro SB, Junior CO, Souza Alves C, Dias AT, Juliano MA, Castañon MC, Almeida MV, Teixeira HC and Ferreira A (2013). Genistein derivatives down-modulates pro-inflammatory cytokines in activated J774A.1 cells and reverses clinical signs of experimental autoimmune encephalomyelitis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00252 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: 12 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Sandra B Castro, Universidade Federal de Juiz de Fora, Parasitologia, Microbiologia e Imunologia, Juiz de Fora, Minas Gerais, 36036-900, Brazil, [email protected] 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 Sandra B Castro Celso O Junior Caio Cesar Souza Alves Alyria T Dias Maria A Juliano Maria C Castañon Mauro V Almeida Henrique C Teixeira Ana Paula Ferreira Google Sandra B Castro Celso O Junior Caio Cesar Souza Alves Alyria T Dias Maria A Juliano Maria C Castañon Mauro V Almeida Henrique C Teixeira Ana Paula Ferreira Google Scholar Sandra B Castro Celso O Junior Caio Cesar Souza Alves Alyria T Dias Maria A Juliano Maria C Castañon Mauro V Almeida Henrique C Teixeira Ana Paula Ferreira PubMed Sandra B Castro Celso O Junior Caio Cesar Souza Alves Alyria T Dias Maria A Juliano Maria C Castañon Mauro V Almeida Henrique C Teixeira Ana Paula Ferreira 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.