Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Lipopolysaccharide (LPS)-Induced Inflammatory Responses in Primary Human Osteoarthritic Fibroblast-Like Synoviocytes
Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Lipopolysaccharide (LPS)-Induced Inflammatory Responses in Primary Human Osteoarthritic Fibroblast-Like Synoviocytes
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瞬时受体电位锚蛋白 1 (TRPA1) 介导脂多糖 (LPS) 诱导的原代人骨关节炎成纤维细胞样滑膜细胞的炎症反应
DOI：
10.1007/s10753-017-0724-0
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发表时间：
2018-01
期刊：
影响因子：
5.1
通讯作者：
王培民
中科院分区：
文献类型：
--
作者：
王培民
摘要瞬时受体电位锚蛋白1 （TRPA1）是一种与膜相关的阳离子通道，广泛表达于神经元和非神经元细胞中。最近，越来越多的证据表明TRPA1在骨关节炎（OA）的疾病进展中起着至关重要的作用。因此，我们旨在研究TRPA1是否介导脂多糖（LPS）诱导的原代人OA成纤维细胞样滑膜细胞（OA- fls）炎症反应。通过聚合酶链反应（PCR）和western blot （WB）检测lps处理的OA-FLS中TRPA1的表达，并通过Ca2+内流检测TRPA1通道的功能。同时，采用免疫分析法检测lps处理细胞中白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、IL-6、基质金属蛋白酶(MMP)-1和MMP-3的产生。对lps诱导的炎性关节炎大鼠进行TRPA1抑制后的组织学观察。LPS诱导后，TRPA1基因和蛋白表达呈时间依赖性或剂量依赖性增加。同时，TRPA1介导的Ca2+内流也在人OA-FLS中增强。此外，TRPA1的药物抑制和基因沉默下调了lps处理的FLS中IL-1β、TNF-α、IL-6、MMP-1和MMP-3的产生。最后，TRPA1拮抗剂也能减轻滑膜炎症和软骨退变。我们发现LPS使TRPA1的功能性表达增加，其激活参与了原发性人OA-FLS的LPS减少炎症反应，抑制TRPA1对LPS诱导的关节炎具有保护作用。
AbstractTransient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal and non-neuronal cells. Recently, emerging evidences suggested the crucial role of TRPA1 in the disease progression of osteoarthritis (OA). Therefore, we aimed to investigate whether TRPA1 mediate lipopolysaccharide (LPS)-induced inflammatory responses in primary human OA fibroblast-like synoviocytes (OA-FLS). The expression of TRPA1 in LPS-treated OA-FLS was assessed by polymerase chain reaction (PCR) and western blot (WB), and the functionality of TRPA1 channel by Ca2+influx measurements. Meanwhile, production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, matrix metalloproteinase (MMP)-1, and MMP-3 in LPS-treated cells was measured by immunoassay. Histological observation after inhibition of TRPA1 was also performed in rats with LPS-induced inflammatory arthritis. After being induced by LPS, the gene and protein expression of TRPA1 was increased in the time-dependent or dose-dependent manner. Meanwhile, Ca2+influx mediated by TRPA1 in human OA-FLS was also enhanced. In addition, pharmacological inhibition and gene silencing of TRPA1 downregulated the production of IL-1β, TNF-α, IL-6, MMP-1, and MMP-3 in LPS-treated FLS. Finally, synovial inflammation and cartilage degeneration were also reduced by the TRPA1 antagonist. We found the LPS caused the increased functional expression of TRPA1, the activation of which involved in LPS-reduced inflammatory responses in primary human OA-FLS, and the inhibition of TRPA1 produces protective effect in LPS-induced arthritis.
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DOI：
10.1074/jbc.m112.361139
发表时间：
2012-09-14
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hatano N;Itoh Y;Suzuki H;Muraki Y;Hayashi H;Onozaki K;Wood IC;Beech DJ;Muraki K
通讯作者：
Muraki K
锌激活损伤感应TRPA1离子通道。
影响因子：
14.8
作者：
Hu, Hongzhen;Bandell, Michael;Petrus, Matt J.;Zhu, Michael X.;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
3.7
作者：
M. Steenvoorden;Ruud A. Bank;H. Ronday;R. Toes;T. Huizinga;Jeroen DeGroot
通讯作者：
M. Steenvoorden;Ruud A. Bank;H. Ronday;R. Toes;T. Huizinga;Jeroen DeGroot
DOI：
10.1073/pnas.0705923104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Trevisani, Marcello;Siemens, Jan;Geppetti, Pierangelo
通讯作者：
Geppetti, Pierangelo
影响因子：
4.1
作者：
Korhonen, R;Kankaanranta, H;Moilanen, E
通讯作者：
Moilanen, E