Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001 |
| |
Authors: | Katalin Kis-Toth Ildiko Bacskai Peter Gogolak Anett Mazlo Istvan Szatmari Eva Rajnavolgyi |
| |
Institution: | 1. Department of Immunology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary;2. Department of Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary;3. Department of Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA, USA |
| |
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. |
| |
Keywords: | DC dendritic cell IDC immature DC MDC mature DC MMP matrix metalloproteinase TIMP tissue inhibitor of matrix metalloproteinase LPS lipopolysaccharide LCH Langerhans cell histiocytosis |
本文献已被 ScienceDirect 等数据库收录! |
|