HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print May 22, 2003

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0203086v1 74/1/88    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pezzato, E. Articles by Garbisa, S. Search for Related Content PubMed PubMed Citation Articles by Pezzato, E. Articles by Garbisa, S.

© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0203086

Received for publication February 28, 2003.
Revised March 7, 2003.
Accepted for publication March 17, 2003.

Article

Proteinase-3 directly activates MMP-2 and degrades gelatin and Matrigel; differential inhibition by (-)epigallocatechin-3-gallate

Elga Pezzato ^*, Massimo Donà ^*, Luigi Sartor ^*, Isabella Dell'Aica ^*, Roberto Benelli , Adriana Albini , and Spiridione Garbisa ^*@

*Department of Experimental Biomedical Sciences, Medical School, Padova, Italy; and Molecular Biology Laboratory, National Institute for Research on Cancer, IST, Genova, Italy

^@ To whom correspondence should be addressed. E-mail: garbisa{at}unipd.it.

	Abstract

Proteinase-3 (PR-3), a serine-proteinase mainly expressed by neutrophils (PMNs), can degrade a variety of extracellular matrix proteins and may contribute to a number of inflammation-triggered diseases. Here, we show that in addition to Matrigel^TM components, PR-3 is also able to degrade denatured collagen and directly activate secreted but not membrane-bound pro-MMP-2, a matrix metallo-proteinase instrumental to cellular invasion. In contrast, following addition of purified PR-3 or PMNs to HT1080 tumor cells, dose-dependent inhibition of in vitro Matrigel^TM invasion is registered. (-)Epigallocatechin-3-gallate (EGCG), the main flavanol in green tea and known to inhibit inflammation and tumor invasion, exerts dose-dependent inhibition of degradation of gelatin (IC₅₀<20 µM) and casein, which is directly triggered by PR-3. The presence of EGCG does not modify the colocalization of MMP-2 and exogenous PR-3 at the cell surface and does not restrain secreted pro-MMP-2 and pro-MMP-9 activation or degradation of a specific, synthetic peptide by PR-3. These results add new activities to the list of those exerted by PR-3 and indicate a differential inhibition as a result of EGCG.

Key Words: neutrophils • gelatinolysis • EGCG

This article has been cited by other articles:

				I. Dell'Aica, L. Sartor, P. Galletti, D. Giacomini, A. Quintavalla, F. Calabrese, C. Giacometti, E. Brunetta, F. Piazza, C. Agostini, et al. Inhibition of Leukocyte Elastase, Polymorphonuclear Chemoinvasion, and Inflammation-Triggered Pulmonary Fibrosis by a 4-Alkyliden-beta-lactam with a Galloyl Moiety J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 539 - 546. [Abstract] [Full Text] [PDF]

				V. M. Adhami, I. A. Siddiqui, N. Ahmad, S. Gupta, and H. Mukhtar Oral Consumption of Green Tea Polyphenols Inhibits Insulin-Like Growth Factor-I-Induced Signaling in an Autochthonous Mouse Model of Prostate Cancer Cancer Res., December 1, 2004; 64(23): 8715 - 8722. [Abstract] [Full Text] [PDF]