Journal of Cell Science 116, e1003 (2003)
Copyright © 2003 The Company of Biologists Limited
A matrix remodeller for inflammation
Tumour-necrosis-factor-stimulated gene 6 encodes a protein (TSG-6) that is
absent in most healthy adult tissue but is synthesized in response to
inflammatory mediators and during inflammation-like processes such as
ovulation. Extracellular matrix (ECM) remodelling is a notable feature of
sites of TSG-6 expression, and TSG-6 has anti-inflammatory and
chondroprotective effects in models of inflammation and arthritis. In a
Commentary on p. 1863,
Caroline Milner and Anthony Day review our understanding of the properties of
this interesting protein. TSG-6 is a secreted protein and contains a Link
module – a domain present in many proteins that bind to the ECM
component hyaluronan. It interacts with the serine protease inhibitor
I
I, which like TSG-6 is a hyaluronanbinding protein. It binds to two
other matrix components: chondroitin 4-sulphate and aggregan. The interaction
with II appears to modulate formation of II-hyaluronan complexes
in the ECM and, independently, enhance the anti-plasmin activity of II
– both of which could be important for ECM remodelling. TSG-6 is also
able to inhibit leukocyte migration during inflammation, perhaps by modulating
adhesion/migration of a specific leukocyte subpopulation.
Related articles in JCS:
- TSG-6: a multifunctional protein associated with inflammation
- Caroline M. Milner and Anthony J. Day
JCS 2003 116: 1863-1873.
[Abstract]
[Full Text]
