Mechanism of TSCS promote anti-Fas antibody-induced FLS apoptosis via blocking MC-tryptase-PAR-2-Rho

来源 :中国药理学与毒理学杂志 | 被引量 : 0次 | 上传用户:yao_huaxin
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
OBJECTIVE It has been supposed that mast cells have important participation in the physiopathology of RA,however,the role of mast cells in the pathogenesis of RA remains unclear.In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts.METHODS Mast cells and fibroblasts synovial were obtained from mouse.Chemical mediator release was assessed by measuringβ-hexosa-minidase release.TSCS and bone marrow-derived mast cells were co-cultured;the toxic effects of TSCS on mast cell was measured by MTT and CCK-8 method;the releasing amount of tryptase in cell supernatants was measured by Elisa assay;the expression of FLS cell membrane receptor PAR-2 was detected by flow cytometry;the apoptosis of FLS cell was detected through flow cytometry and Western blotting;the level of activated Rho-GTP was detected by the pull-down method and Western blotting.RESULTS In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts,and found that tryptase significantly increased the expression of PAR-2 on the surface of fibroblast-like synovial cell,significantly activated Rho kinase,significantly inhibited apoptosis of fibroblast-like synovial cell induced by CH11.The release rates ofβ-hexosaminidase and the level of tryptase from bone marrow-derived mast cells after stimulation with different antigen and co-cultured with TSCS significantly decreased compared to the control group.In the co-culture system of mast cells and fibroblast-like synovial cells,TSCS treatment significantly inhibited Rho kinase(P<0.05),significantly promoted apoptosis of fibroblast-like synovial cell induced by CH11(P<0.05).CONCLUSION These results demonstrate that tryptase may play a key role in the physiopathology of RA.TSCS can inhibit mast cells activation and promote FLS cells apoptosis.This provide theoretical and experimental basis for the study of mast cells as targets for new anti-RA drugs. OBJECTIVE It has been been that mast cells have important participation in the physiopathology of RA, however, the role of mast cells in the pathogenesis of RA remains unclear. In this study, we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts. METHODS Mast cells and fibroblasts synovial were obtained from mouse. Chemical mediator release was assessed by measuring β-hexosa-minidase release. TSCS and bone marrow-derived mast cells were co-cultured; the toxic effects of TSCS on mast cell was measured by The expression of FLS cell membrane receptor PAR-2 ​​was detected by flow cytometry; the apoptosis of FLS cell was detected through flow cytometry and Western blotting ; the level of activated Rho-GTP was detected by the pull-down method and Western blotting .RESULTS In this study, we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts, and found that tryptase significantly increased the expression of PAR-2 ​​on the surface of fibroblast-like synovial cells, significantly activated Rho kinase, significantly regulated apoptosis of fibroblast-like synovial cell induced by CH11. hexosaminidase and the level of tryptase from bone marrow-derived mast cells after stimulation with different antigen and co-cultured with TSCS significantly decreased compared to the control group. the co-culture system of mast cells and fibroblast-like synovial cells, TSCS treatment significantly promoted apoptosis of fibroblast-like synovial cell induced by CH11 (P <0.05) .CONCLUSION These results demonstrate that tryptase may play a key role in the physiopathology of RA. TSCS can inhibit mast cells activation and promote FLS cells apoptosis. this provide theoretical and experimental basis for the study of mast cells as targets for new anti-RA drugs.
其他文献
科特迪瓦于1960年独立,自称是自由国家,坚持以自由资本主义为发展方向。经济发展较快,有相当长的一段时间保持了较快的增长势头,曾被誉为经济发展的“橱窗”、“样板”,但由
结构调整在使国民经济结构趋于优化、宏观经济效益得到提高的同时,会带来社会各阶层、各集团、各单位以及个人的利益格局的调整,处置不当会产生不稳定因素。在我国的结构调整
一、前言工业烧碱中铁含量的测定有硫氰酸盐法,磺基水杨酸法,2·2′——联吡啶法,和1·10——菲啰啉法等。这些方法都具有操作简便,快速等特点。其中1.10——菲啰啉法还有颜
合成了题目化合物,并用X射线单晶衍射法测定结构。其晶体学参数:空间群:P_1~-,a=14.118(3)A,b=14.453(3)A,c=16.392(4)A,a=111.60(2)°,β=93.75(2)°,γ=117.10(1)°,V=2656
岩石矿物分析(以下简称岩矿分析)历来是分析化学的重要组成部分。从广义上讲,土壤是岩石风化的产物,水系以及其他一些沉积物也是岩石矿物迁移搬运后的产物,地下水也是一种矿
李芝芬等人测定了盐在甲醇混合溶剂中的溶解度,得到经验公式: logs_0/s_s=kx_Ne (1)式中s_0和s_s分别为盐在甲醇和混合溶剂中的溶解度,x_Ne为第二组分溶剂的摩尔分数,k为第
稀土催化体系合成顺式1,4-聚丁二烯的研究表明,还原组分一氢二异丁基铝(HAl)优于三异丁基铝(Al)。唐学明等认为,对镍系催化体系丁二烯聚合,当Al中含有一定HAl时,对丁二烯聚
英国的激光器测量系统可用于涡轮叶片点蚀的精确测量。喷气发动机涡轮叶片点蚀的检验对维修工程师来说是一个很头痛的问题。在航空运输中,保证安全是最重要的,如果点蚀严重,
微量稀土元素能促使农作物高产,但是长期广泛使用稀土肥料对人类和动物是否安全?到今天仍然是含糊不清的问题,也是学术界争论的问题。农业方面的人士认为:根据稀土的致死量
我厂原使用的轧辊预热器是1954年由苏联引进的设备,采用工频电感应加热,轧辊被加热的温度低,1962年以前一直是低温装辊;当轧辊温度提高到300℃左右时,方可轧制薄规格钢板,这