| First Author | Tsutsui H | Year | 1999 |
| Journal | Immunity | Volume | 11 |
| Issue | 3 | Pages | 359-67 |
| PubMed ID | 10514014 | Mgi Jnum | J:57879 |
| Mgi Id | MGI:1345908 | Doi | 10.1016/s1074-7613(00)80111-9 |
| Citation | Tsutsui H, et al. (1999) Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity 11(3):359-67 |
| abstractText | 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. |
