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Title: A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization.
Authors: Wen, Guanmei
Zhang, Cheng
Chen, Qishan
Luong, Le Anh
Mustafa, Arif
Ye, Shu
Xiao, Qingzhong
First Published: 19-Jun-2015
Publisher: American Society for Biochemistry and Molecular Biology
Citation: Journal of Biological Chemistry, 2015, 290 (31), pp. 19158-19172
Abstract: Matrix metalloproteinase-8 (MMP8) has been shown to influence various cellular functions. As monocytes and macrophages (Mφ) express MMP8, we investigated if MMP8 played a role in macrophage differentiation and polarization. MMP8 expression was significantly increased during monocyte differentiation into Mφ. Monocyte-derived Mφ from MMP8-deficient mice expressed higher levels of M1-Mφ markers but lower levels of M2-Mφ markers than monocyte-derived Mφ from wild-type mice. Although Mφ from either MMP8-deficient or wild-type mice were inducible by interferon-γ into M1-Mφ, only wild-type Mφ but not MMP8-deficient Mφ could be induced into M2-Mφ by interleukin-4. However, MMP8-deficient Mφ exposed to conditioned culture media of wild-type Mφ developed a M2-Mφ phenotype. Compared with conditioned culture media of wild-type Mφ, conditioned culture media of MMP8-deficient Mφ contained a lower concentration of active transforming growth factor-β (TGF-β), an M2-Mφ inducer. Moreover, evidence also showed that the degradation of the TGF-β sequester, fibromodulin, was modulated by MMP8. The data indicate a previously unknown role of MMP8 in M2-Mφ polarization by cleaving fibromodulin and therefore increasing the bioavailability of the M2-Mφ inducer TGF-β.
DOI Link: 10.1074/jbc.M114.634022
ISSN: 0021-9258
eISSN: 1083-351X
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, American Society for Biochemistry and Molecular Biology. Deposited with reference to the publisher’s open access archiving policy.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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