A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization.

Guanmei Wen, Cheng Zhang, Qishan Chen, Le Anh Luong, Arif Mustafa, Shu Ye, Qingzhong Xiao

The Journal of biological chemistry 2015 Jul 31

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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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Guanmei Wen, Cheng Zhang, Qishan Chen, Le Anh Luong, Arif Mustafa, Shu Ye, Qingzhong Xiao. A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization. The Journal of biological chemistry. 2015 Jul 31;290(31):19158-72