A novel tylophorine analog NK-007 ameliorates colitis through inhibition of innate immune response.
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| Abstract |
In this study, we synthesized (±)-tylophorine malate (NK-007), an analog of tylophorine (DCB3503), and analyzed its anti-inflammatory effect in vivo using a dextran sulfate sodium (DSS)-induced colitis model and an acetic acid-induced colitis model. As indicated by disease activity index (DAI) and degree of macroscopic colonic damage, NK-007 can significantly suppress colitis. To delineate the underlying mechanism, we have explored the influence of NK-007 on the production of TNF-α by murine primary bone marrow-derived dendritic cells (BMDCs) as well as monocyte/macrophage cell line Raw 264.7 triggered by lipopolysaccharide (LPS). For both types of innate immune cells, NK-007 showed a potent TNF-α inhibitory effect, and has in addition reduced the expression of IL-12 in BMDCs. Moreover, Raw cells treated with NK-007 also showed decreased phosphorylation of NF-κB, which may explain the protective immune-regulatory effect of NK-007 for experimental colitis.
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| Authors | Ti Wen, Yangguang Li, Meng Wu, Xi Chen, Lin Han, Xiucong Bao, Ziwen Wang, Kailiang Wang, Yanna Hu, Xinglong Zhou, Zhenzhou Wu, Puyue Wang, Zhangyong Hong, Liqing Zhao, Qingmin Wang, Zhinan Yin |
| Journal | International immunopharmacology (Int Immunopharmacol) Vol. 14 Issue 4 Pg. 487-94 (Dec 2012) ISSN: 1878-1705 [Electronic] Netherlands |
| PMID | 22929538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2012 Elsevier B.V. All rights reserved. |
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