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

被引：18

作者：

Kis-Toth, Katalin ^{[1
,3
]}

Bacskai, Ildiko ^{[1
]}

Gogolak, Peter ^{[1
]}

Mazlo, Anett ^{[1
]}

Szatmari, Istvan ^{[2
]}

Rajnavolgyi, Eva ^{[1
]}

机构：

[1] Univ Debrecen, Dept Immunol, Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary

[2] Univ Debrecen, Dept Biochem & Mol Biol, Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary

[3] Beth Israel Deaconess Med Ctr, Dept Rheumatol, Boston, MA 02215 USA

来源：

IMMUNOBIOLOGY | 2013年 / 218卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

CD1a; Dendritic cell; Immunotherapy; Matrix metalloproteinase; Tissue inhibitor of matrix; metalloproteinase; NECROSIS-FACTOR-ALPHA; CD34(+) HEMATOPOIETIC PROGENITORS; CORD BLOOD DIFFERENTIATE; IN-VIVO; TISSUE INHIBITORS; PPAR-GAMMA; ANTIGEN PRESENTATION; GELATINASE-B; MIGRATION; EXPRESSION;

D O I：

10.1016/j.imbio.2013.06.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2013 Elsevier GmbH. All rights reserved.

引用

页码：1361 / 1369

页数：9

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