title: Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001.
abstract: Matrix metalloproteinases (MMPs) are endopeptidases with the potential to cleave extracellular matrix, support tissue renewal and regulate cell migration. Functional activities of MMPs are regulated by tissue inhibitors of MMPs (TIMPs) and disruption of the MMP-TIMP balance has pathological consequences. Here we studied the expression and secretion of MMPs and TIMPs in CD1a(-) and CD1a(+) monocyte-derived dendritic cell (DC) subpopulations. Our results showed that monocytes express TIMPs but lack MMPs, whereas upon differentiation to moDCs and in response to activation signals the expression of MMPs is increased and that of TIMPs is decreased. MMP-9 is expressed dominantly in the CD1a(-) subpopulation, while MMP-12 is preferentially expressed in CD1a(+) cells. Experiments performed with the synthetic MMP inhibitor GM6001 revealed that this drug efficiently inhibits the migration of moDCs through inactivation of MMPs. We conclude that modulation of MMP activity by GM6001 emerges as a novel approach to manipulate DC migration under inflammatory conditions.
authors.affiliation: Department of Immunology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; Department of Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: katakt@gmail.com.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: Ildiko
authors.initials: I
authors.lastname: Bacskai
authors.forename: Peter
authors.initials: P
authors.lastname: Gogolak
authors.forename: Anett
authors.initials: A
authors.lastname: Mazlo
authors.forename: Istvan
authors.initials: I
authors.lastname: Szatmari
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D009000:Monocytes; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12
keywords: CD1a; DC; Dendritic cell; IDC; Immunotherapy; LCH; LPS; Langerhans cell histiocytosis; MDC; MMP; Matrix metalloproteinase; TIMP; Tissue inhibitor of matrix metalloproteinase; dendritic cell; immature DC; lipopolysaccharide; matrix metalloproteinase; mature DC; tissue inhibitor of matrix metalloproteinase