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The TNF-\u03b1 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.<\/jats:p>","DOI":"10.4049\/jimmunol.179.5.2686","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:46Z","timestamp":1397848666000},"page":"2686-2689","source":"Crossref","is-referenced-by-count":278,"title":["Cutting Edge: TNF-\u03b1-Converting Enzyme (TACE\/ADAM17) Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock"],"prefix":"10.1093","volume":"179","author":[{"given":"Keisuke","family":"Horiuchi","sequence":"first","affiliation":[{"name":"Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Department of Medicine and Department of Physiology and Biophysics, Weill Medical College of Cornell University , New York, NY 10021"},{"name":"Department of Orthopedic Surgery, Keio University, School of Medicine , Tokyo ,","place":["Japan"]},{"name":"Department of Anti-Aging Orthopedic Research, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokuhiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Keio University, School of Medicine , Tokyo ,","place":["Japan"]},{"name":"Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironari","family":"Takaishi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Toyama","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Keio University, School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl P","family":"Blobel","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Department of Medicine and Department of Physiology and Biophysics, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2026012809352817800_R1","first-page":"745","volume-title":"Nat. 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