角鲨烯可诱导巨噬细胞自噬，促进STAT1-IRF1-TLR3通路及关节炎的发生。
Pristane induces autophagy in macrophages, promoting a STAT1-IRF1-TLR3 pathway and arthritis.
作者信息
Zhu Wenhua, Xu Jing, Jiang Congshan, Wang Bo, Geng Manman, Wu Xiaoying, Hussain Nazim, Gao Ning, Han Yan, Li Dongmin, Lan Xi, Ning Qilan, Zhang Fujun, Holmdahl Rikard, Meng Liesu, Lu Shemin
机构信息
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China.
出版信息
Clin Immunol. 2017 Feb;175:56-68. doi: 10.1016/j.clim.2016.11.017. Epub 2016 Dec 7.
Autophagy is involved in both innate and adaptive immune regulation. We propose that autophagy regulates activation of TLR3 in macrophages and is thereby essential for development of pristane-induced arthritis. We found that pristane treatment induced autophagy in macrophages in vitro and in vivo, in spleen cells from pristane injected rats. The induced autophagy was associated with STAT1 phosphorylation and expression of IRF1 and TLR3. Blocking the pristane activated autophagy by Wortmannin and Bafilomycin A1 or by RNAi of Becn1 led to a downregulation of the associated STAT1-IRF1-TLR3 pathway. Most importantly, the development of arthritis was alleviated by suppressing either autophagy or TLR3. We conclude that pristane enhanced autophagy, leading to a STAT1-IRF1 controlled upregulation of TLR3 expression in macrophages, is a pathogenic mechanism in the development of arthritis.
自噬参与天然免疫和适应性免疫调节。我们提出，自噬调节巨噬细胞中TLR3的激活，因此对于 pristane 诱导的关节炎的发展至关重要。我们发现，pristane 处理在体外和体内均可诱导巨噬细胞自噬，在注射 pristane 的大鼠的脾细胞中也是如此。诱导的自噬与 STAT1 磷酸化以及 IRF1 和 TLR3 的表达相关。用渥曼青霉素和巴弗洛霉素 A1 或通过 Beclin1 的 RNA 干扰阻断 pristane 激活的自噬会导致相关的 STAT1-IRF1-TLR3 通路下调。最重要的是，通过抑制自噬或 TLR3 可减轻关节炎的发展。我们得出结论，pristane 增强自噬，导致巨噬细胞中 STAT1-IRF1 控制的 TLR3 表达上调，是关节炎发展的致病机制。
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