Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models.

作者: Dominik Schreiber , Lisa Marx , Silke Felix , Jasmin Clasohm , Maximilian Weyland

DOI: 10.3389/FPHYS.2017.00566

关键词:

摘要: Inflammatory bowel diseases (IBD), which include Crohn´s disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or colonic mucosal layer. Current therapies aiming to suppress exaggerated immune response in IBD largely rely on compounds with non-satisfying effects side-effects. Therefore, new therapeutical options needed. In present study, we investigated anti-inflammatory of fungal metabolites, galiellalactone dehydrocurvularin both an vitro intestinal inflammation model, as well isolated myenteric plexus enterocyte cells. Administration a pro-inflammatory cytokine mix through mesenteric artery segments caused up-regulation marker genes. Treatment murine by application significantly prevented expression genes mRNA protein level. Comparable results perfused intestine treatment primary enteric nervous system (ENS) cells from reduced cytokines such IL-6, TNF-α, IL-1β enzymes COX-2 iNOS levels. Similar metabolites were observed human colorectal adenocarcinoma cell line DLD-1 after stimulation IFN-γ (10 ng/ml), TNF-α ng/ml) (5 ng/ml). Our show mesenterially model provides reliable tool for screening therapeutics limited amounts test compounds. Furthermore could characterize two novel active compounds, interesting candidates studies animal models IBD.

参考文章(60)
Mari Hämäläinen, Riikka Lilja, Hannu Kankaanranta, Eeva Moilanen, Inhibition of iNOS expression and NO production by anti-inflammatory steroids: Reversal by histone deacetylase inhibitors Pulmonary Pharmacology & Therapeutics. ,vol. 21, pp. 331- 339 ,(2008) , 10.1016/J.PUPT.2007.08.003
Nai-Ning Song, Intestinal permeability of metformin using single-pass intestinal perfusion in rats. World Journal of Gastroenterology. ,vol. 12, pp. 4064- 4070 ,(2006) , 10.3748/WJG.V12.I25.4064
H. F. Otto, P. Möller, F. Momburg, K. Koretz, Sequential induction of MHC antigens on autochthonous cells of ileum affected by Crohn's disease. American Journal of Pathology. ,vol. 129, pp. 493- 502 ,(1987)
Atsushi Mizoguchi, Animal Models of Inflammatory Bowel Disease Progress in Molecular Biology and Translational Science. ,vol. 105, pp. 263- 320 ,(2012) , 10.1016/B978-0-12-394596-9.00009-3
Yasuhisa Adachi, Hiroshi Suzuki, Yuichi Sugiyama, Quantitative evaluation of the function of small intestinal P-glycoprotein: comparative studies between in situ and in vitro. Pharmaceutical Research. ,vol. 20, pp. 1163- 1169 ,(2003) , 10.1023/A:1025088628787
Christian Bogdan, Nitric oxide and the immune response Nature Immunology. ,vol. 2, pp. 907- 916 ,(2001) , 10.1038/NI1001-907
å. v. Keita, J. D. Söderholm, The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterology and Motility. ,vol. 22, pp. 718- 733 ,(2010) , 10.1111/J.1365-2982.2010.01498.X
Karel Geboes, Paul Rutgeerts, Nadine Ectors, Jos Mebis, Freddy Penninckx, Gaston Vantrappen, Valeer J. Desmet, Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease Gastroenterology. ,vol. 103, pp. 439- 447 ,(1992) , 10.1016/0016-5085(92)90832-J
Dominik H. Schreiber, Gerhard Erkel, Karl-Herbert Schäfer, Mo1801 A Model of In Vitro Perfused Mouse Intestine Suitable for Pharmacological Testing of Anti-Inflammatory Drugs Gastroenterology. ,vol. 142, ,(2012) , 10.1016/S0016-5085(12)62654-7
Mohd Aftab Alam, Fahad Ibrahim Al-Jenoobi, Abdullah M. Al-mohizea, Everted gut sac model as a tool in pharmaceutical research: limitations and applications Journal of Pharmacy and Pharmacology. ,vol. 64, pp. 326- 336 ,(2012) , 10.1111/J.2042-7158.2011.01391.X