Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo

Hiroyasu Ito, Kazuki Ando, Toshinori Nakayama, Masaru Taniguchi, Takayuki Ezaki, Kuniaki Saito, Masao Takemura, Kenji Sekikawa, Michio Imawari, Mitsuru Seishima, Hisataka Moriwaki

Research output: Contribution to journalArticle

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Abstract

Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by α-galactosylceramide (α-GalCer) on murine liver regeneration using Vα 14 NKT knockout (Jα 281-/-) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in Jα 281+/+ but not in Jα 281-/- mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) γ and tumor necrosis factor α (TNF-α) messenger RNA (mRNA) after stimulation with both factors in Jα 281+/+ mice. Either anti-IFN-γ or TNF-α antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-α injection similarly caused injury in hepatectomized livers of both Jα 281+/+ and Jα 281-/- mice; indeed, adoptively transferred TNF-α+/+ NKT cells enhanced liver injury after hepatectomy in TNF-α knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-α synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration.

Original languageEnglish
Pages (from-to)1116-1124
Number of pages9
JournalHepatology
Volume38
Issue number5
DOIs
Publication statusPublished - 01-01-2003
Externally publishedYes

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Liver Regeneration
Natural Killer Cells
Tumor Necrosis Factor-alpha
T-Lymphocytes
Liver
Hepatectomy
Hepatocytes
Tumor Necrosis Factor Receptors
Wounds and Injuries
Interleukin-12
Interferons
Galactosylceramides
Natural Killer T-Cells
Alanine Transaminase
Knockout Mice
Messenger RNA
Injections
Antibodies
Serum

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Ito, H., Ando, K., Nakayama, T., Taniguchi, M., Ezaki, T., Saito, K., ... Moriwaki, H. (2003). Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo. Hepatology, 38(5), 1116-1124. https://doi.org/10.1053/jhep.2003.50471
Ito, Hiroyasu ; Ando, Kazuki ; Nakayama, Toshinori ; Taniguchi, Masaru ; Ezaki, Takayuki ; Saito, Kuniaki ; Takemura, Masao ; Sekikawa, Kenji ; Imawari, Michio ; Seishima, Mitsuru ; Moriwaki, Hisataka. / Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo. In: Hepatology. 2003 ; Vol. 38, No. 5. pp. 1116-1124.
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abstract = "Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by α-galactosylceramide (α-GalCer) on murine liver regeneration using Vα 14 NKT knockout (Jα 281-/-) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in Jα 281+/+ but not in Jα 281-/- mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) γ and tumor necrosis factor α (TNF-α) messenger RNA (mRNA) after stimulation with both factors in Jα 281+/+ mice. Either anti-IFN-γ or TNF-α antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-α injection similarly caused injury in hepatectomized livers of both Jα 281+/+ and Jα 281-/- mice; indeed, adoptively transferred TNF-α+/+ NKT cells enhanced liver injury after hepatectomy in TNF-α knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-α synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration.",
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Ito, H, Ando, K, Nakayama, T, Taniguchi, M, Ezaki, T, Saito, K, Takemura, M, Sekikawa, K, Imawari, M, Seishima, M & Moriwaki, H 2003, 'Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo', Hepatology, vol. 38, no. 5, pp. 1116-1124. https://doi.org/10.1053/jhep.2003.50471

Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo. / Ito, Hiroyasu; Ando, Kazuki; Nakayama, Toshinori; Taniguchi, Masaru; Ezaki, Takayuki; Saito, Kuniaki; Takemura, Masao; Sekikawa, Kenji; Imawari, Michio; Seishima, Mitsuru; Moriwaki, Hisataka.

In: Hepatology, Vol. 38, No. 5, 01.01.2003, p. 1116-1124.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of Vα 14 NKT Cells in the Development of Impaired Liver Regeneration In Vivo

AU - Ito, Hiroyasu

AU - Ando, Kazuki

AU - Nakayama, Toshinori

AU - Taniguchi, Masaru

AU - Ezaki, Takayuki

AU - Saito, Kuniaki

AU - Takemura, Masao

AU - Sekikawa, Kenji

AU - Imawari, Michio

AU - Seishima, Mitsuru

AU - Moriwaki, Hisataka

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by α-galactosylceramide (α-GalCer) on murine liver regeneration using Vα 14 NKT knockout (Jα 281-/-) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in Jα 281+/+ but not in Jα 281-/- mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) γ and tumor necrosis factor α (TNF-α) messenger RNA (mRNA) after stimulation with both factors in Jα 281+/+ mice. Either anti-IFN-γ or TNF-α antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-α injection similarly caused injury in hepatectomized livers of both Jα 281+/+ and Jα 281-/- mice; indeed, adoptively transferred TNF-α+/+ NKT cells enhanced liver injury after hepatectomy in TNF-α knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-α synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration.

AB - Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by α-galactosylceramide (α-GalCer) on murine liver regeneration using Vα 14 NKT knockout (Jα 281-/-) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in Jα 281+/+ but not in Jα 281-/- mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) γ and tumor necrosis factor α (TNF-α) messenger RNA (mRNA) after stimulation with both factors in Jα 281+/+ mice. Either anti-IFN-γ or TNF-α antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-α injection similarly caused injury in hepatectomized livers of both Jα 281+/+ and Jα 281-/- mice; indeed, adoptively transferred TNF-α+/+ NKT cells enhanced liver injury after hepatectomy in TNF-α knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-α synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration.

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