Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice

M. Imamura, H. Tsutsui, K. Yasuda, R. Uchiyama, S. Yumikura-Futatsugi, K. Mitani, S. Hayashi, S Akira, S. Taniguchi, N. van Rooijen, J. Tschopp, T. Yamamoto, J. Fujimoto, K. Nakanishi

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background/Aims: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. Methods:Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. Results: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. Conclusions: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved
Original languageUndefined/Unknown
Pages (from-to)333-341
JournalJournal of Hepatology
Volume51
Issue number2
DOIs
Publication statusPublished - 2009

Cite this

Imamura, M., Tsutsui, H., Yasuda, K., Uchiyama, R., Yumikura-Futatsugi, S., Mitani, K., ... Nakanishi, K. (2009). Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice. Journal of Hepatology, 51(2), 333-341. https://doi.org/10.1016/j.jhep.2009.03.027
Imamura, M. ; Tsutsui, H. ; Yasuda, K. ; Uchiyama, R. ; Yumikura-Futatsugi, S. ; Mitani, K. ; Hayashi, S. ; Akira, S ; Taniguchi, S. ; van Rooijen, N. ; Tschopp, J. ; Yamamoto, T. ; Fujimoto, J. ; Nakanishi, K. / Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice. In: Journal of Hepatology. 2009 ; Vol. 51, No. 2. pp. 333-341.
@article{592428c506644400aa3fd73f9887401c,
title = "Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice",
abstract = "Background/Aims: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. Methods:Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. Results: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. Conclusions: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved",
author = "M. Imamura and H. Tsutsui and K. Yasuda and R. Uchiyama and S. Yumikura-Futatsugi and K. Mitani and S. Hayashi and S Akira and S. Taniguchi and {van Rooijen}, N. and J. Tschopp and T. Yamamoto and J. Fujimoto and K. Nakanishi",
year = "2009",
doi = "10.1016/j.jhep.2009.03.027",
language = "Undefined/Unknown",
volume = "51",
pages = "333--341",
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Imamura, M, Tsutsui, H, Yasuda, K, Uchiyama, R, Yumikura-Futatsugi, S, Mitani, K, Hayashi, S, Akira, S, Taniguchi, S, van Rooijen, N, Tschopp, J, Yamamoto, T, Fujimoto, J & Nakanishi, K 2009, 'Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice' Journal of Hepatology, vol. 51, no. 2, pp. 333-341. https://doi.org/10.1016/j.jhep.2009.03.027

Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice. / Imamura, M.; Tsutsui, H.; Yasuda, K.; Uchiyama, R.; Yumikura-Futatsugi, S.; Mitani, K.; Hayashi, S.; Akira, S; Taniguchi, S.; van Rooijen, N.; Tschopp, J.; Yamamoto, T.; Fujimoto, J.; Nakanishi, K.

In: Journal of Hepatology, Vol. 51, No. 2, 2009, p. 333-341.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice

AU - Imamura, M.

AU - Tsutsui, H.

AU - Yasuda, K.

AU - Uchiyama, R.

AU - Yumikura-Futatsugi, S.

AU - Mitani, K.

AU - Hayashi, S.

AU - Akira, S

AU - Taniguchi, S.

AU - van Rooijen, N.

AU - Tschopp, J.

AU - Yamamoto, T.

AU - Fujimoto, J.

AU - Nakanishi, K.

PY - 2009

Y1 - 2009

N2 - Background/Aims: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. Methods:Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. Results: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. Conclusions: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

AB - Background/Aims: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. Methods:Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. Results: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. Conclusions: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

U2 - 10.1016/j.jhep.2009.03.027

DO - 10.1016/j.jhep.2009.03.027

M3 - Article

VL - 51

SP - 333

EP - 341

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 2

ER -