Ketotifen fumarate attenuates feline gingivitis related with gingival microenvironment modulation

文献类型： 外文期刊

第一作者： Yuan, Weifeng

作者： Yuan, Weifeng;Hou, Shaohua;Jia, Hong;Liang, Lin;Sui, Xiukun;Zhao, Xinghui;Zhao, Zhanzhong;Qiu, Zhizhao;Liu, Tao;Chen, Xinsheng;Li, Hongjun;Sun, Yanchen

作者机构：

关键词： Ketotifen fumarate; Gingivitis; Gingival microenvironment; Mast cells; Macrophages

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.932； 五年影响因子：4.624 ）

ISSN： 1567-5769

年卷期： 2018 年 65 卷

页码：

收录情况： SCI

摘要： Gingivitis is evidenced by inflammation of the free gingiva, and still reversible. If left untreated, it may then progress to periodontitis. In the present study, the therapeutical effect of ketotifen fumarate on gingivitis was explored. Domestic cats with varying degrees of gingivitis naturally were enrolled in this study. Subgroups of animals were treated twice daily for one week with or without ketotifen fumarate (5 mg/kg). Effects of ketotifen fumarate were measured on gingival index, cells accumulation, mediators release, receptor-ligand interaction, oxidative stress, MAPK and NF-kappa B pathways, epithelial barrier and apoptosis. Ketotifen fumarate attenuated the initiation and progression of gingivitis, inhibited the infiltrations of mast cells, B lymphocytes, T lymphocytes, macrophages, neutrophils and eosinophils as well as the release of IgE, beta-hexosaminidase, tryptase, chymase, TNF-alpha, IL-4, and IL-beta, influenced endothelial cells, fibroblasts and epithelial cells proliferation and apoptosis, and induced Th2 cells polarization, where ketotifen fumarate also might affect their interactions. Ketotifen fumarate reduced the oxidative stress, and inhibited NF-kappa B and p38 MAPK related with mast cells and macrophages accumulation. Ketotifen fumarate improved the aberrant expression of ZO-1 and inhibits the following apoptosis. On the other hand, these cells and mediators augmented functional attributes of them involving SCF/c-Kit, alpha 4137/VCAM-1 and IL-8/IL-8RB interactions, thus creating a positive feedback loop to perpetuate gingivitis, where an inflammation microenvironment was modeled. Our results showed a previously unexplored therapeutic potential of ketotifen fumarate for gingivitis and further suggest that, in addition to biofilms, targeting inflammation microenvironment could be new strategy for the treatment of gingivitis/periodontitis.

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