Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD), the fatal side effects of bone marrow transplantation, was shown to be accompanied by elevation of serum levels of interleukin 18 (IL-18). In this study, the mechanism underlying the accumulation of IL-18 in aGVHD in mice was investigated. Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes demonstrated aGVHD and contained markedly elevated serum levels of IL-18. In contrast, recipients having transplantation with gld/gld spleen cells, which lack functional Fas ligand (FasL), contained only normal ranges of IL-18, indicating FasL-mediated IL-18 release in aGVHD. The wild-type hosts engrafted with caspase-1-deficient cells revealed marked increases of IL-18 similar to those engrafted with wild-type cells, whereas caspase-1-deficient recipients engrafted with wild-type cells showed only a slight elevation of serum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggest FasL-mediated caspase-1-dependent IL-18 secretion in aGVHD in mice.
Itoi
H
H
Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Fujimori
Y
Y
Tsutsui
H
H
Matsui
K
K
Futatsugi
S
S
Okamura
H
H
Hara
H
H
Hada
T
T
Kakishita
E
E
Nakanishi
K
K
D000208:Acute Disease; D000818:Animals; D020170:Caspase 1 / Q000494:pharmacology*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D016378:Tissue Transplantation / Q000009:adverse effects
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D020170:Caspase 1