Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001

Katalin Kis-Toth, Ildiko Bacskai, Peter Gogolak, Anett Mazlo, Istvan Szatmari, Eva Rajnavolgyi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1361-1369
Number of pages9
JournalImmunobiology
Volume218
Issue number11
DOIs
Publication statusPublished - Nov 1 2013

Keywords

  • CD1a
  • Dendritic cell
  • Immunotherapy
  • Matrix metalloproteinase
  • Tissue inhibitor of matrix metalloproteinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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