| First Author | Horiuchi K | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 5 | Pages | 2686-9 |
| PubMed ID | 17709479 | Mgi Jnum | J:139846 |
| Mgi Id | MGI:3810234 | Doi | 10.4049/jimmunol.179.5.2686 |
| Citation | Horiuchi K, et al. (2007) Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J Immunol 179(5):2686-9 |
| abstractText | TNF-alpha, 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-alpha 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. |
