Lin Yang, Luo Zhengqiang
Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FEBS Lett. 2017 Apr;591(8):1141-1149. doi: 10.1002/1873-3468.12622. Epub 2017 Mar 30.
In the present study, we investigated the role of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in rheumatoid arthritis (RA) and explored the underlying mechanism. We found that both mRNA and protein levels of NLRP6 are attenuated in synovial tissues and fibroblast-like synoviocytes (FLS) of RA patients compared to patients with osteoarthritis. We also observed that pro-inflammatory cytokine production is decreased and nuclear factor-kappa B activation is inhibited in NLRP6-overexpressing RA-FLS. Furthermore, we found that NLRP6 overexpression promotes transforming growth factor-b-activated kinase 1-binding protein 2/3 lysosome-dependent degradation, and we provide evidence showing that NLRP6 plays the role of providing the docking site to facilitate the interaction between transforming growth factor-b-activated kinase 1-binding protein 2/3 and tripartite motif 38 in RA-FLS.
在本研究中，我们调查了含吡啶结构域的核苷酸寡聚化结构域样受体家族6（NLRP6）在类风湿关节炎（RA）中的作用，并探索其潜在机制。我们发现，与骨关节炎患者相比，RA患者滑膜组织和成纤维样滑膜细胞（FLS）中NLRP6的mRNA和蛋白质水平均降低。我们还观察到，在过表达NLRP6的RA-FLS中，促炎细胞因子的产生减少，核因子-κB的激活受到抑制。此外，我们发现NLRP6过表达促进转化生长因子-β激活激酶1结合蛋白2/3的溶酶体依赖性降解，并且我们提供的证据表明，在RA-FLS中，NLRP6起到提供对接位点的作用，以促进转化生长因子-β激活激酶1结合蛋白2/3与三联基序38之间的相互作用。
