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Cutting Edge: TNF-α-Converting Enzyme (TACE/ADAM17) Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock
| Content Provider | Scilit |
|---|---|
| Author | Horiuchi, Keisuke Kimura, Tokuhiro Miyamoto, Takeshi Takaishi, Hironari Okada, Yasunori Toyama, Yoshiaki Blobel, Carl P. |
| Copyright Year | 2007 |
| Description | TNF-α, a potent proinflammatory cytokine, is synthesized as a membrane-anchored precursor and proteolytically released from cells. Soluble TNF is the primary mediator of pathologies such as rheumatoid arthritis, Crohn's disease, and endotoxin shock. The TNF-α converting enzyme (TACE), a disintegrin and metalloprotease 17 (ADAM17), has emerged as the best candidate TNF sheddase, but other proteinases can also release TNF. Because TACE-deficient mice die shortly after birth, we generated conditional TACE-deficient mice to address whether TACE is the relevant sheddase for TNF in adult mice. In this study, we report that TACE inactivation in myeloid cells or temporal inactivation at 6 wk offers strong protection from endotoxin shock lethality in mice by preventing increased TNF serum levels. These findings corroborate that TACE is the major endotoxin-stimulated TNF sheddase in mouse myeloid cells in vivo, thereby further validating TACE as a principal target for the treatment of TNF-dependent pathologies. |
| Ending Page | 2689 |
| Page Count | 4 |
| Starting Page | 2686 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.179.5.2686 |
| Journal | The Journal of Immunology |
| Issue Number | 5 |
| Volume Number | 179 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2007-09-01 |
| Access Restriction | Open |
| Subject Keyword | Lethality From Endotoxin Shock |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
