Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

See all formats and pricing
More options …
Volume 382, Issue 10


Secretion of Gelatinases and Activation of Gelatinase A (MMP-2) by Human Rheumatoid Synovial Fibroblasts

H. Smolian / A. Aurer / M. Sittinger / J. Zacher / J.-P. Bernimoulin / G.-R. Burmester / H. Kolkenbrock
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2001.183


In monolayer cultures human rheumatoid synovial fibroblasts (HRSF) secrete gelatinase A (MMP-2) and, unlike other human fibroblasts, to a minor extent also gelatinase B (MMP-9) as inactive proenzymes. In this regard HRSF resemble the fibrosarcoma cell line HT-1080. Unlike HT-1080, however, HRSF do not increase the secretion of MMP-9 in response to phorbol-12-myristate-13-acetate. This indicates that in HRSF the protein kinase C pathway for an enhanced MMP-9 secretion is inactive. None of the substances used in our study increased MMP-9 secretion, but some of them inhibited MMP-9 secretion. The secretion of MMP-2 could not be enhanced either, not even by dbcAMP, which has been reported to be effective in Sertoli and peritubular cells. Activation of MMP-2 in HRSF could be induced by treatment with concanavalin A (ConA) or cytochalasin D, as was shown for other cell types. This activation was not accompanied by a significant change in the amount of secreted TIMP-1 and TIMP-2. In contrast to reports on human skin fibroblasts, however, the activation of MMP-2 could not be induced in HRSF by treatment of the cells with monensin or sodium orthovanadate. Moreover, monensin was shown to act as an inhibitor of ConA or cytochalasin Dmediated activation. Additionally, and in contrast to a report on a rat fibroblast cell line, MMP-2 activation is not mediated via the MAP kinase pathway in HRSF: PD 98059, a specific inhibitor of MAP kinase kinase, did not inhibit the activation of MMP-2. Similarly ineffective were PD 169316, an inhibitor for p38 MAP kinase, other inhibitors for protein kinases as lavendustin A, Gö 6983, wortmannin, rapamycin, as well as the protein tyrosine kinase inhibitors herbimycin A and genistein. Only staurosporin, a broad spectrum inhibitor of protein kinases, and the ionophores monensin and A 23187 effectively inhibited MMP-2 activation in HRSF. Our results demonstrate that MMP-2 can be activated by quite different pathways, and that different cells, even when belonging to the fibroblast family, do not necessarily use the same activating pathways.

About the article

Published Online: 2005-06-01

Published in Print: 2001-10-15

Citation Information: Biological Chemistry, Volume 382, Issue 10, Pages 1491–1499, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2001.183.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Adam Al-Kashi, Trinidad Montero-Melendez, Niloufar Moradi-Bidhendi, James P. Gilligan, Nozer Mehta, Mauro Perretti, and John Wallace
PLoS ONE, 2013, Volume 8, Number 2, Page e54299
Gerd R. Burmester, Eugen Feist, and Thomas Dörner
Nature Reviews Rheumatology, 2013, Volume 10, Number 2, Page 77
Patricia Saravia-Otten, Teresa Frisan, Monica Thelestam, and José María Gutiérrez
Toxicon, 2004, Volume 44, Number 7, Page 749
Yoshihiro Wada, Kohei Shimada, Tomio Kimura, and Shigeru Ushiyama
Immunology Letters, 2005, Volume 101, Number 1, Page 50
Anthony L. Newsome, Jon Paul Johnson, Rebecca L. Seipelt, and Michael W. Thompson
Biochemistry and Cell Biology, 2007, Volume 85, Number 5, Page 563
Georgios Tsilingaridis, Tülay Yucel-Lindberg, and Thomas Modéer
Acta Odontologica Scandinavica, 2003, Volume 61, Number 3, Page 154
S. Sandya, M. A. Achan, and P. R. Sudhakaran
Indian Journal of Clinical Biochemistry, 2009, Volume 24, Number 1, Page 42
Sophie Flood, Rheinallt Parri, Anwen Williams, Victor Duance, and Deborah Mason
Arthritis & Rheumatism, 2007, Volume 56, Number 8, Page 2523
Rosario García-Vicuña, Maria Victoria Gómez-Gaviro, Maria Jesús Domínguez-Luis, Martina K. Pec, Isidoro González-Alvaro, Jose María Alvaro-Gracia, and Federico Díaz-González
Arthritis & Rheumatism, 2004, Volume 50, Number 12, Page 3866

Comments (0)

Please log in or register to comment.
Log in