Cutting edge

TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock

Keisuke Horiuchi, Tokuhiro Kimura, Takeshi Miyamoto, Hironari Takaishi, Yasunori Okada, Yoshiaki Toyama, Carl P. Blobel

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2686-2689
Number of pages4
JournalJournal of Immunology
Volume179
Issue number5
Publication statusPublished - 2007 Sep 1

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Disintegrins
Metalloproteases
Myeloid Cells
Endotoxins
Shock
Pathology
Crohn Disease
Rheumatoid Arthritis
Peptide Hydrolases
ADAM17 Protein
Parturition
Cytokines
Membranes
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Horiuchi, K., Kimura, T., Miyamoto, T., Takaishi, H., Okada, Y., Toyama, Y., & Blobel, C. P. (2007). Cutting edge: TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. Journal of Immunology, 179(5), 2686-2689.

Cutting edge : TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. / Horiuchi, Keisuke; Kimura, Tokuhiro; Miyamoto, Takeshi; Takaishi, Hironari; Okada, Yasunori; Toyama, Yoshiaki; Blobel, Carl P.

In: Journal of Immunology, Vol. 179, No. 5, 01.09.2007, p. 2686-2689.

Research output: Contribution to journalArticle

Horiuchi, K, Kimura, T, Miyamoto, T, Takaishi, H, Okada, Y, Toyama, Y & Blobel, CP 2007, 'Cutting edge: TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock', Journal of Immunology, vol. 179, no. 5, pp. 2686-2689.
Horiuchi K, Kimura T, Miyamoto T, Takaishi H, Okada Y, Toyama Y et al. Cutting edge: TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. Journal of Immunology. 2007 Sep 1;179(5):2686-2689.
Horiuchi, Keisuke ; Kimura, Tokuhiro ; Miyamoto, Takeshi ; Takaishi, Hironari ; Okada, Yasunori ; Toyama, Yoshiaki ; Blobel, Carl P. / Cutting edge : TNF-α-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. In: Journal of Immunology. 2007 ; Vol. 179, No. 5. pp. 2686-2689.
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