Wen et al, J Biol Chem 2015.pdf (3.63 MB)
A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization.
journal contributionposted on 2017-07-14, 14:21 authored by Guanmei Wen, Cheng Zhang, Qishan Chen, Le Anh Luong, Arif Mustafa, Shu Ye, Qingzhong Xiao
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.
This work was supported by British Heart Foundation Grants FS/09/044/28007, PG/11/40/28891, PG/13/45/30326, and PG/15/11/31279.
CitationJournal of Biological Chemistry, 2015, 290 (31), pp. 19158-19172
Author affiliation/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences
- VoR (Version of Record)
Published inJournal of Biological Chemistry
PublisherAmerican Society for Biochemistry and Molecular Biology
extracellular matrix proteininflammationmacrophagemacrophage polarizationmatrix metalloproteinase (MMP)matrix metalloproteinase-8transforming growth factor β (TGF-β)AnimalsCell DifferentiationCell LineCell PolarityExtracellular Matrix ProteinsFibromodulinGene Expression Regulation, EnzymologicInterleukin-4MacrophagesMatrix Metalloproteinase 8Mice, Inbred C57BLMice, KnockoutProteoglycansProteolysisSignal TransductionTransforming Growth Factor beta1Up-Regulation