title: A novel tylophorine analog NK-007 ameliorates colitis through inhibition of innate immune response.
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.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Wen
authors.forename: Yangguang
authors.initials: Y
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Xiucong
authors.initials: X
authors.lastname: Bao
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Kailiang
authors.initials: K
authors.lastname: Wang
authors.forename: Yanna
authors.initials: Y
authors.lastname: Hu
authors.forename: Xinglong
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Puyue
authors.initials: P
authors.lastname: Wang
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Hong
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhao
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003598:Cytoskeletal Proteins; D016264:Dextran Sulfate / Q000633:toxicity; D007113:Immunity, Innate / Q000187:drug effects*; D007212:Indolizines / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D015394:Molecular Structure; D010616:Phenanthrenes / Q000627:therapeutic use*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003598:Cytoskeletal Proteins; D007212:Indolizines; D008840:Microfilament Proteins; C576415:NK-007; D010616:Phenanthrenes; D010750:Phosphoproteins; C066559:Lcp1 protein, mouse; D016264:Dextran Sulfate; D019342:Acetic Acid