help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on July 27, 2006, doi:10.1165/rcmb.2006-0018OC

Am. J. Respir. Cell Mol. Biol., Volume 36, Number 1, January 2007, 20-31

A more recent version of this article appeared on January 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2006-0018OCv1
36/1/20    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Forteza, R.
Right arrow Articles by Day, A. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Forteza, R.
Right arrow Articles by Day, A. J

Submitted on January 17, 2006
Revised on July 25, 2006

TSG-6 Potentiates the Anti Tissue Kallikrein Activity of Inter-{alpha}-inhibitor through Bikunin Release

Rosanna Forteza1*, Susana M Casalino-Matsuda1, Maria Elena Monzon1, Erik Fries2, Marilyn S Rugg3, Caroline M Milner3, and Anthony J Day4

1 Division of Pulmonary and Critical Care Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA, 2 Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Uppsala, Sweden, 3 Department of Biochemistry, MRC Immunochemistry Unit, University of Oxford, Oxford, United Kingdom, 4 Department of Biochemistry, MRC Immunochemistry Unit, University of Oxford, Oxford, United Kingdom; Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

* To whom correspondence should be addressed. E-mail: rforteza{at}miami.edu.

TSG-6 (the protein product of TNF-stimulated gene-6), an inflammation-associated protein, forms covalent complexes with heavy chains (HC) from inter-{alpha}-inhibitor (I{alpha}I) and pre-{alpha}-inhibitor (P{alpha}I), and associates non-covalently with their common bikunin chain, potentiating the anti-plasmin activity of this serine protease inhibitor. Here we show that TSG-6 and TSG-6[[rad]]HC complexes are present in bronchoalveolar lavage from asthmatics and increase following allergen challenge. Immunodetection demonstrated elevated TSG-6 in airway tissue and secretions of smokers. Experiments conducted in vitro with purified components revealed that bikunin[[rad]]HC complexes (byproducts of TSG-6[[rad]]HC formation) release bikunin. Immunoprecipitation revealed that bikunin accounts for a significant proportion of tissue kallikrein inhibition in BAL after allergen challenge but not in baseline conditions, confirming that bikunin in its free state, but not when associated with HCs, is a relevant protease inhibitor in airway secretions. In primary cultures of differentiated human airway epithelial and submucosal gland cells TSG-6 is induced by TNF-{alpha} and IL-1{beta} pointing towards those cells as responsible for TSG-6 release in vivo. Bikunin and HC3 (i.e., P{alpha}I) were also induced by TNF-{alpha} in primary cultures. Our results suggest that TSG-6 may play an important protective role in bronchial epithelium by increasing the antiprotease screen on the airway lumen.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
D. J. Mahoney, K. Mikecz, T. Ali, G. Mabilleau, D. Benayahu, A. Plaas, C. M. Milner, A. J. Day, and A. Sabokbar
TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation
J. Biol. Chem., September 19, 2008; 283(38): 25952 - 25962.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. W. Sanggaard, C. S. Sonne-Schmidt, T. P. Krogager, K. A. Lorentzen, H.-G. Wisniewski, I. B. Thogersen, and J. J. Enghild
The Transfer of Heavy Chains from Bikunin Proteins to Hyaluronan Requires Both TSG-6 and HC2
J. Biol. Chem., July 4, 2008; 283(27): 18530 - 18537.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. D. Blundell, D. J. Mahoney, M. R. Cordell, A. Almond, J. D. Kahmann, A. Perczel, J. D. Taylor, I. D. Campbell, and A. J. Day
Determining the Molecular Basis for the pH-dependent Interaction between the Link Module of Human TSG-6 and Hyaluronan
J. Biol. Chem., April 27, 2007; 282(17): 12976 - 12988.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2006 American Thoracic Society. 		  2009/2010 ATS Fellows Career Development Awards