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

First Author  Wen G Year  2015
Journal  J Biol Chem Volume  290
Issue  31 Pages  19158-72
PubMed ID  26092731 Mgi Jnum  J:315857
Mgi Id  MGI:6832184 Doi  10.1074/jbc.M114.634022
Citation  Wen G, et al. (2015) A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization. J Biol Chem 290(31):19158-72
abstractText  Matrix metalloproteinase-8 (MMP8) has been shown to influence various cellular functions. As monocytes and macrophages (Mphi) express MMP8, we investigated if MMP8 played a role in macrophage differentiation and polarization. MMP8 expression was significantly increased during monocyte differentiation into Mphi. Monocyte-derived Mphi from MMP8-deficient mice expressed higher levels of M1-Mphi markers but lower levels of M2-Mphi markers than monocyte-derived Mphi from wild-type mice. Although Mphi from either MMP8-deficient or wild-type mice were inducible by interferon-gamma into M1-Mphi, only wild-type Mphi but not MMP8-deficient Mphi could be induced into M2-Mphi by interleukin-4. However, MMP8-deficient Mphi exposed to conditioned culture media of wild-type Mphi developed a M2-Mphi phenotype. Compared with conditioned culture media of wild-type Mphi, conditioned culture media of MMP8-deficient Mphi contained a lower concentration of active transforming growth factor-beta (TGF-beta), an M2-Mphi inducer. Moreover, evidence also showed that the degradation of the TGF-beta sequester, fibromodulin, was modulated by MMP8. The data indicate a previously unknown role of MMP8 in M2-Mphi polarization by cleaving fibromodulin and therefore increasing the bioavailability of the M2-Mphi inducer TGF-beta.
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