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Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice
Open accessAbstract
IL-18, produced as a biologically inactive precursor, is processed by caspase-1 in LPS-activated macrophages. Here, we investigated caspase-1-independent processing of IL-18 in Fas ligand (FasL)-stimulated macrophages and its involvement in liver injury. Administration of Propionibacterium acnes (P. acnes) upregulated functional Fas expression on macrophages in an IFNgamma-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with FasL. This was also the case for caspase-1-deficient mice. Administration of recombinant soluble FasL (rFasL) after P. acnes priming induced comparable elevation of serum IL-18 in parallel with elevated serum liver enzyme levels. However, liver injury was not induced in IL-18-deficient mice after rFasL administration. These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury.
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Citations
Cited by
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466
Interleukin-18 Regulates Both Th1 and Th2 Responses
Nakanishi, K., Yoshimoto, T., Tsutsui, H., & Okamura, H. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.423 · Cited by 1,315
Self-citationHistorical insights into cytokines
Dinarello, C. A. (2007) · European Journal of Immunology · doi:10.1002/eji.200737772 · Cited by 926
Kawaguchi, M., Takahashi, M., Hata, T., Kashima, Y., Usui, F., Morimoto, H., Izawa, A., Takahashi, Y., Masumoto, J., Koyama, J., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.982777 · Cited by 884
Rodrigues, T. S., de Sá, K. S. G., Ishimoto, A. Y., Becerra, A., Oliveira, S., Almeida, L., Gonçalves, A. V., Perucello, D. B., Andrade, W. A., Castro, R., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201707 · Cited by 839
Metadata
- Authors
- Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S.-I., Hada, T., Akira, S., Yagita, H., Okamura, H., & Nakanishi, K.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 11
- Issue
- 3
- Pages
- 359-367
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2033300203
- Cited by
- 243
- References
- 0
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S.-I., Hada, T., Akira, S., Yagita, H., Okamura, H., & Nakanishi, K. (1999). Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice. Immunity. https://doi.org/10.1016/s1074-7613(00)80111-9
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