Journal
INFLAMMATION
Volume 39, Issue 3, Pages 974-985Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-016-0324-4
Keywords
Angptl7; inflammation; P38 MAPK; RAW264.7 cells; TNF-alpha; macrophage
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Funding
- National Key Basic Research Program of China [2012CB124702]
- 948 Program [2012-S13, 2013-S15]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110146130002]
- Program of National Natural Science Foundation of China [31172093]
- National Science Foundation for Fostering Talents in Basic Research [J1103510]
- Fundamental Research Funds for the Central Universities [2013PY005]
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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-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-10, and transforming growth factor beta 1 (TGF-beta 1)) 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-beta 1 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-alpha 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.
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