Zhao Jingjing, Liu Juntian, Pang Xiaoming, Wang Shuyue, Wu Di, Zhang Xiaolu, Feng Liuxin
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Cell Physiol Biochem. 2013;32(3):569-80. doi: 10.1159/000354461. Epub 2013 Sep 6.
C-reactive protein (CRP) participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II) is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The present study observed effect of Ang II on CRP expression and the related signal pathway in hepatocytes.
mRNA and protein expressions in human hepatocytes were determined with RT-PCR and Western blot respectively. Reactive oxygen species (ROS) was measured using a fluorescence probe. CRP in liver and serum of rats was determined by immunohistochemistry and ELISA respectively.
Ang II induced mRNA and protein expression of CRP in hepatocytes and increased CRP production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II-stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2. Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore, pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression.
Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo through AT1 receptor followed by ROS, MAPK and NF-κB signal pathway.
C反应蛋白（CRP）参与炎症性疾病的发展。肝细胞是循环CRP的主要来源。尽管已知血管紧张素II（Ang II）可引发炎症反应，但Ang II是否诱导肝细胞中CRP的表达仍不清楚。本研究观察了Ang II对肝细胞中CRP表达及相关信号通路的影响。
分别采用RT-PCR和Western blot检测人肝细胞中的mRNA和蛋白表达。使用荧光探针测定活性氧（ROS）。分别通过免疫组织化学和ELISA测定大鼠肝脏和血清中的CRP。
Ang II诱导肝细胞中CRP的mRNA和蛋白表达，增加肝脏中CRP的产生及血清中CRP水平。氯沙坦降低Ang II诱导的肝细胞中CRP表达。氯沙坦和噻吩甲酰三氟丙酮降低Ang II刺激的ROS产生。N-乙酰半胱氨酸拮抗Ang II诱导的CRP表达。氯沙坦和N-乙酰半胱氨酸抑制Ang II激活的ERK1/2。与ERK1/2不同，只有氯沙坦抑制Ang II激活的JNK。此外，吡咯烷二硫代氨基甲酸盐消除Ang II诱导的CRP表达。
Ang II能够通过AT1受体，继而经ROS、MAPK和NF-κB信号通路在体外和体内诱导肝细胞中CRP的表达。
