title: A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization.
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.
authors.affiliation: From the Centre for Clinical Pharmacology and the Department of Pathophysiology, Guangzhou Medical University, 510182 Guangzhou, China, and.
authors.forename: Guanmei
authors.initials: G
authors.lastname: Wen
authors.affiliation: From the Centre for Clinical Pharmacology and the Department of Thoracic Surgery and Cardio Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: From the Centre for Clinical Pharmacology and.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: From the Centre for Clinical Pharmacology and.
authors.forename: Le Anh
authors.initials: le A
authors.lastname: Luong
authors.affiliation: Biological Service Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
authors.forename: Arif
authors.initials: A
authors.lastname: Mustafa
authors.affiliation: From the Centre for Clinical Pharmacology and sy127@le.ac.uk.
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
authors.affiliation: From the Centre for Clinical Pharmacology and q.xiao@qmul.ac.uk.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000071235:Fibromodulin; D015971:Gene Expression Regulation, Enzymologic; D015847:Interleukin-4 / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D020784:Matrix Metalloproteinase 8 / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011509:Proteoglycans / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D015854:Up-Regulation
chemical_list: D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; D000071235:Fibromodulin; D015847:Interleukin-4; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8
keywords: extracellular matrix protein; inflammation; macrophage; macrophage polarization; matrix metalloproteinase (MMP); matrix metalloproteinase-8; transforming growth factor β (TGF-β)