The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals

Kenjirou Kamezaki, Kazuya Shimoda, Akihiko Numata, Tadashi Matsuda, Kei Ichi Nakayama, Mine Harada

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Abstract

Mice lacking Tyk2, Stat1 or Stat4, which are members of the Jak-Stat signaling cascade, were resistant to LPS-induced endotoxin shock. Interestingly, Tyk2-deficient mice had higher resistance to LPS challenge than mice lacking either Stat1 or Stat4. The activation of MAPK and NF-κB by LPS, and the production of TNF-α and IL-12 after LPS injection, were not abrogated by the absence of Tyk2, Stat1 or Stat4 In Stat1-deficient mice, the induction of IFN-β by LPS in macrophages was severely reduced, although the serum level of IFN-γ was elevated after LPS injection. In contrast, in Stat-4 deficient mice, the induction of IFN-β by LPS was normal, but the serum level of IFN-γ remained low after LPS injection. Interestingly, the induction of both IFN-β and IFN-γ by LPS was severely reduced in Tyk2-deficient mice. Therefore, Stat1 and Stat4 independently play substantial roles in the susceptibility to LPS. Tyk2 is essential for LPS-induced endotoxin shock, and this signaling pathway is transduced by the activation of Stat1 and Stat4.

Original languageEnglish
Pages (from-to)1173-1179
Number of pages7
JournalInternational immunology
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 1 2004

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Endotoxins
Injections
Shock
Interleukin-12
Serum
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. / Kamezaki, Kenjirou; Shimoda, Kazuya; Numata, Akihiko; Matsuda, Tadashi; Nakayama, Kei Ichi; Harada, Mine.

In: International immunology, Vol. 16, No. 8, 01.08.2004, p. 1173-1179.

Research output: Contribution to journalArticle

Kamezaki, Kenjirou ; Shimoda, Kazuya ; Numata, Akihiko ; Matsuda, Tadashi ; Nakayama, Kei Ichi ; Harada, Mine. / The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. In: International immunology. 2004 ; Vol. 16, No. 8. pp. 1173-1179.
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