The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smookler, D. S.
Right arrow Articles by Khokha, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smookler, D. S.
Right arrow Articles by Khokha, R.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
The Journal of Immunology, 2006, 176: 721-725.
Copyright © 2006 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Tissue Inhibitor of Metalloproteinase 3 Regulates TNF-Dependent Systemic Inflammation

David S. Smookler, Fazilat F. Mohammed, Zamaneh Kassiri, Gordon S. Duncan, Tak W. Mak and Rama Khokha1

Ontario Cancer Institute, University Health Network, Toronto, Canada

Host response to infectious agents must be rapid and powerful. One mechanism is the release of presynthesized membrane-bound TNF. TNF shedding is mediated by TNF-{alpha} converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3). We show that loss of TIMP3 impacts innate immunity by dysregulating cleavage of TNF and its receptors. Cultured timp3–/– macrophages release more TNF in response to LPS than wild-type macrophages. In timp3–/– mice, LPS causes serum levels of TNF and its receptors to rise more rapidly and remain higher compared with wild-type mice. The altered kinetics of ligand and receptor shedding enhances TNF signaling in timp3–/– mice, indicated by elevated serum IL-6. Physiologically, timp3–/– mice are more susceptible to LPS-induced mortality. Ablation of the TNF receptor gene p55 (Tnfrsf1a) or treatment with a synthetic metalloproteinase inhibitor rescues timp3–/– mice. Thus, TIMP3 is essential for normal innate immune function.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
Z. Kassiri, V. Defamie, M. Hariri, G. Y. Oudit, S. Anthwal, F. Dawood, P. Liu, and R. Khokha
Simultaneous Transforming Growth Factor {beta}-Tumor Necrosis Factor Activation and Cross-talk Cause Aberrant Remodeling Response and Myocardial Fibrosis in Timp3-deficient Heart
J. Biol. Chem., October 23, 2009; 284(43): 29893 - 29904.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. Sakimoto, A. Yamada, and M. Sawa
Release of Soluble Tumor Necrosis Factor Receptor 1 from Corneal Epithelium by TNF-{alpha}-Converting Enzyme-Dependent Ectodomain Shedding
Invest. Ophthalmol. Vis. Sci., October 1, 2009; 50(10): 4618 - 4621.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
I. Vanlaere and C. Libert
Matrix Metalloproteinases as Drug Targets in Infections Caused by Gram-Negative Bacteria and in Septic Shock
Clin. Microbiol. Rev., April 1, 2009; 22(2): 224 - 239.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Wang, A. H. Herrera, Y. Li, K. K. Belani, and B. Walcheck
Regulation of Mature ADAM17 by Redox Agents for L-Selectin Shedding
J. Immunol., February 15, 2009; 182(4): 2449 - 2457.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
G. Cai, X. Zhang, Q. Hong, F. Shao, X. Shang, B. Fu, Z. Feng, H. Lin, J. Wang, S. Shi, et al.
Tissue inhibitor of metalloproteinase-1 exacerbated renal interstitial fibrosis through enhancing inflammation
Nephrol. Dial. Transplant., June 1, 2008; 23(6): 1861 - 1875.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Alper, R. Laws, B. Lackford, W. A. Boyd, P. Dunlap, J. H. Freedman, and D. A. Schwartz
Identification of innate immunity genes and pathways using a comparative genomics approach
PNAS, May 13, 2008; 105(19): 7016 - 7021.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Ali and V. Knauper
Phorbol Ester-induced Shedding of the Prostate Cancer Marker Transmembrane Protein with Epidermal Growth Factor and Two Follistatin Motifs 2 Is Mediated by the Disintegrin and Metalloproteinase-17
J. Biol. Chem., December 28, 2007; 282(52): 37378 - 37388.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. Pottier, C. Chupin, V. Defamie, B. Cardinaud, R. Sutherland, G. Rios, F. Gauthier, P. J. Wolters, Y. Berthiaume, P. Barbry, et al.
Relationships between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis: A Role for Dipeptidyl-Peptidase I and Tissue Inhibitor of Metalloproteinase-3?
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1098 - 1107.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Serino, R. Menghini, L. Fiorentino, R. Amoruso, A. Mauriello, D. Lauro, P. Sbraccia, M. L. Hribal, R. Lauro, and M. Federici
Mice Heterozygous for Tumor Necrosis Factor-{alpha} Converting Enzyme Are Protected From Obesity-Induced Insulin Resistance and Diabetes
Diabetes, October 1, 2007; 56(10): 2541 - 2546.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Horiuchi, T. Kimura, T. Miyamoto, H. Takaishi, Y. Okada, Y. Toyama, and C. P. Blobel
Cutting Edge: TNF-{alpha}-Converting Enzyme (TACE/ADAM17) Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock
J. Immunol., September 1, 2007; 179(5): 2686 - 2689.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.