Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, July the 26th 2016, 07:00-10:00

ZORA's new graphical user interface will be relaunched (For further infos watch out slideshow ZORA: Neues Look & Feel). There will be short interrupts on ZORA Service between 07:00am and 10:00 am. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-16313

Distler, J H W; Jüngel, A; Huber, L C; Seemayer, C A; Reich, C F; Gay, R E; Michel, B A; Fontana, A; Gay, S; Pisetsky, D S; Distler, O (2005). The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 102(8):2892-2897.

[img] PDF - Registered users only
View at publisher


Rheumatoid arthritis is a chronic inflammatory disease characterized by destruction of cartilage and bone that is mediated by synovial fibroblasts. To determine the mechanisms by which these cells are activated to produce matrix metalloproteinases (MMPs), the effects of microparticles were investigated. Microparticles are small membrane-bound vesicles whose release from immune cells is increased during activation and apoptosis. Because microparticles occur abundantly in the synovial fluid in rheumatoid arthritis, they could represent novel stimulatory agents. Microparticles derived from T cells and monocytes strongly induced the synthesis of MMP-1, MMP-3, MMP-9, and MMP-13 in fibroblasts. The induction was time-dependent, with effects primarily observed after 36 h; under these conditions, MMP-2, MMP-14, and tissue inhibitor of MMP-1 (TIMP-1), TIMP-2, and TIMP-3 were not induced. Microparticles also increased the synthesis of inflammatory mediators including IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and MCP-2. In Ikappa-B-transfected synovial fibroblasts, MMPs were less inducible by microparticles compared with wild-type fibroblasts. Blocking of TNFalpha and IL-1beta with antibodies against TNFalpha and with IL-1 receptor antagonist did not abrogate stimulation by microparticles. These data provide evidence for a novel mechanism by which vesicles derived from activated or apoptotic immune cells can promote the destructive activity of synovial fibroblasts in rheumatoid arthritis.


147 citations in Web of Science®
162 citations in Scopus®
Google Scholar™



2 downloads since deposited on 08 Apr 2009
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:610 Medicine & health
Deposited On:08 Apr 2009 14:15
Last Modified:05 Apr 2016 13:06
Publisher:National Academy of Sciences
Additional Information:Copyright: National Academy of Sciences USA
Publisher DOI:10.1073/pnas.0409781102
PubMed ID:15701693

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page