title: Angiopoietin-Like Protein 7 Promotes an Inflammatory Phenotype in RAW264.7 Macrophages Through the P38 MAPK Signaling Pathway.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Qian
authors.affiliation: 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.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Yiduo
authors.initials: Y
authors.lastname: He
authors.affiliation: 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. yangzq@mail.hzau.edu.cn.
authors.forename: Zaiqing
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000502:physiology*; D000818:Animals; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C000599407:ANGPTL7 protein, mouse; D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angptl7; P38 MAPK; RAW264.7 cells; TNF-α; inflammation; macrophage