QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Werner, E. Articles by Werb, Z. Search for Related Content PubMed PubMed Citation Articles by Werner, E. Articles by Werb, Z.

Phagocytosis mediated by Yersinia invasin induces collagenase-1 expression in rabbit synovial fibroblasts through a proinflammatory cascade

Erica Werner^1,*, Farrah Kheradmand^1,, Ralph R. Isberg² and Zena Werb^1,

¹ Department of Anatomy, University of California, San Francisco, CA 94143-0452, USA
² Department of Microbiology and Molecular Biology, Tufts University School of Medicine, Boston, MA 02111, USA
^* Present address: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
Present address: Department of Medicine, Baylor College of Medicine, Houston, TX 77025, USA

Author for correspondence (e-mail: zena{at}itsa.ucsf.edu)

Accepted June 7, 2001

We show that the interaction of the Yersinia surface protein, invasin, with rabbit synovial fibroblasts mediates bead phagocytosis and induces expression of interleukin 1 (IL-1), tumor necrosis factor- (TNF-) and MMP-1/collagenase-1 (CL-1). Presentation of invasin as a ligand on the surface of 4.5 µm beads induced phagocytosis and increased CL-1 expression 20-fold after 24 hours. By contrast, presentation of invasin as a spreading substrate did not induce CL-1 expression. CL-1 induction following phagocytosis of invasin-coated beads was mediated by a mechanism dependent on high-affinity binding to ß1 integrins and the function of the small GTPase RhoA. Expression of a function-perturbing mutant, RhoAN19, abrogated bead-induced CL-1 expression. RhoA activation coupled bead phagocytosis with signal transduction because expression of constitutively active mutant RhoV14 was sufficient to trigger CL-1 expression. The signal-transduction cascade elicited by bead phagocytosis triggered NFB activation, stimulating a proinflammatory cellular response with transient increases in TNF- production that peaked at 2 hours and induction of IL-1 that was sustained for at least 10 hours. Inhibition of IL-1 function by blocking antibodies or IL-1 receptor antagonist showed that IL-1 is the autocrine intermediary for subsequent CL-1 induction.

Key words: Yersinia, Invasin, MMP-1, Collagenase, RhoA, Integrin, Phagocytosis, Proinflammatory, Interleukin 1

This article has been cited by other articles:

				E. Werner and Z. Werb Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases J. Cell Biol., June 1, 2002; (2002) 200111028. [Abstract] [Full Text] [PDF]

				P. J. Bruce-Staskal, C. L. Weidow, J. J. Gibson, and A. H. Bouton Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake J. Cell Sci., January 7, 2002; 115(13): 2689 - 2700. [Abstract] [Full Text] [PDF]