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Angiopoietin-Like Protein 7 Promotes an Inflammatory Phenotype in RAW264.7 Macrophages Through the P38 MAPK Signaling Pathway

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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.

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Acknowledgments

This work was supported by grants from the National Key Basic Research Program of China (2012CB124702), the 948 Program (2012-S13 and 2013-S15), the Specialized Research Fund for the Doctoral Program of Higher Education (20110146130002), the Program of National Natural Science Foundation of China (31172093), the National Science Foundation for Fostering Talents in Basic Research (J1103510), and the Fundamental Research Funds for the Central Universities (2013PY005).

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Authors and Affiliations

  1. 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

    Tao Qian, Kun Wang, Jiesheng Cui, Yiduo He & Zaiqing Yang

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  1. Tao Qian
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Correspondence to Zaiqing Yang.

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Highlights

- Angptl7 overexpression induces a pro-inflammatory phenotype in RAW264.7 cells.

- Angptl7 overexpression inhibits TGF-β and glucocorticoid pathways in RAW264.7 cells.

- The P38 MAPK signaling pathway mediates Angptl7-associated inflammatory functions in RAW264.7 cells.

- Intraperitoneal injection of TNF-α induces Angptl7 expression in mouse eyes.

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Qian, T., Wang, K., Cui, J. et al. Angiopoietin-Like Protein 7 Promotes an Inflammatory Phenotype in RAW264.7 Macrophages Through the P38 MAPK Signaling Pathway. Inflammation 39, 974–985 (2016). https://doi.org/10.1007/s10753-016-0324-4

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