Qian Tao, Wang Kun, Cui Jiesheng, He Yiduo, Yang Zaiqing
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
Inflammation. 2016 Jun;39(3):974-85. doi: 10.1007/s10753-016-0324-4.
Angiopoietin-like protein 7 (Angptl7) has been extensively studied for decades, but its potential immune functions have not been characterized. Hence, we investigated the relationship between Angptl7 and inflammation by using RAW264.7 monocyte/macrophage cells. The expression of genes encoding inflammation-associated factors cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-10, and transforming growth factor beta 1 (TGF-β1)) decreased after RAW264.7 cells were treated with anti-Angptl7 polyclonal antibody but increased after the cells were transfected with an Angptl7-expressing plasmid. Angptl7 overexpression enhanced phagocytosis and inhibited the proliferation of RAW264.7 cells. In addition, Angptl7 antagonized the anti-inflammatory effects of TGF-β1 and dexamethasone. Pathway analysis showed that Angptl7 promoted the phosphorylation of both p65 and p38, but only the P38 mitogen-activated protein kinase (MAPK) signaling pathway mediated Angptl7-associated inflammatory functions. Additionally, after 1 week of daily intraperitoneal injections of recombinant TNF-α in a mouse model of peripheral inflammation, Angptl7 expression increased in the mouse eyes. Thus, Angptl7 is a factor that promotes pro-inflammatory responses in macrophages through the P38 MAPK signaling pathway and represents a potential therapeutic target for treatment of inflammatory diseases.
几十年来，血管生成素样蛋白7（Angptl7）一直受到广泛研究，但其潜在的免疫功能尚未得到明确阐述。因此，我们利用RAW264.7单核细胞/巨噬细胞研究了Angptl7与炎症之间的关系。在用抗Angptl7多克隆抗体处理RAW264.7细胞后，编码炎症相关因子环氧合酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、IL-10和转化生长因子β1（TGF-β1）的基因表达下降，但在用表达Angptl7的质粒转染细胞后，这些基因的表达增加。Angptl7过表达增强了吞噬作用并抑制了RAW264.7细胞的增殖。此外，Angptl7拮抗了TGF-β1和地塞米松的抗炎作用。通路分析表明，Angptl7促进了p65和p38的磷酸化，但只有P38丝裂原活化蛋白激酶（MAPK）信号通路介导了与Angptl7相关的炎症功能。此外，在小鼠外周炎症模型中每日腹腔注射重组TNF-α 1周后，小鼠眼中Angptl7的表达增加。因此，Angptl7是一种通过P38 MAPK信号通路促进巨噬细胞促炎反应的因子，是治疗炎症性疾病的潜在治疗靶点。
