Caspase-1, caspase-8, and calpain are dispensable for IL-33 release by macrophages.
In addition to IL-1 and IL-18, IL-33 was recently identified as a member of the IL-1 cytokine family. rIL-33 can promote production of Th2-type cytokines by Th2 cells and mast cells in vitro. Administration of rIL-33 to mice results in increases in IgE secretion and eosinophilic inflammation. However, the precise immune cell source of IL-33 remains unclear. Moreover, although recombinant pro-IL-33 is cleaved by recombinant caspase-1 in vitro, as are pro-IL-1beta and pro-IL-18, the involvement of caspase-1 in pro-IL-33 cleavage remains controversial. In this study, we show that mouse peritoneal macrophages, but not splenic dendritic cells, produced IL-33 upon stimulation with LPS. Likewise, mouse bone marrow cell-derived cultured mast cells also produced a small, but significant amount of IL-33 via FcepsilonRI cross-linking, but not in response to stimulation with LPS. To our surprise, IL-33 release was found even in caspase-1-deficient, caspase-8 inhibitor-treated, and calpain inhibitor-treated macrophages. These observations suggest that caspase-1-, caspase-8-, and calpain-independent IL-33 production by macrophages and/or mast cells may contribute to the pathogenesis of Th2-type allergic inflammation.
Ohno
Tatsukuni
T
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Oboki
Keisuke
K
Kajiwara
Naoki
N
Morii
Eiichi
E
Aozasa
Katsuyuki
K
Flavell
Richard A
RA
Okumura
Ko
K
Saito
Hirohisa
H
Nakae
Susumu
S
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002154:Calpain / Q000502:physiology; D020170:Caspase 1 / Q000502:physiology; D053181:Caspase 8 / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology
C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000067596:Interleukin-33; D007378:Interleukins; D002154:Calpain; D053181:Caspase 8; D020170:Caspase 1