Characterization of ST2 transgenic mice with resistance to IL-33.
IL-33, a member of the IL-1 family, activates MAPK and NF-kappaB through its receptor ST2L and IL-1RAcP. ST2, a member of the IL-1R superfamily, is a secreted form of ST2 gene products, which has been shown to act as a decoy receptor for IL-33 and to inhibit the IL-33/ST2L/IL-1RAcP signaling pathway. In this work, we generated ST2 transgenic mice. In control mice, intraperitoneal administration of IL-33 caused an increased number of eosinophils in blood and in peritoneal cavity, an increased number of peritoneal M Phi, splenomegaly, accumulation of periodic acid-Schiff-positive material in the lung, and high concentrations of serum IL-5 and IL-13. However, these alterations were hardly detectable in ST2 Tg mice. In peritoneal M Phi from IL-33-stimulated mice, mRNA expression of M2 M Phi marker genes were increased compared with thioglycollate-elicited peritoneal M Phi. The IL-33-stimulation also increased the secretion of IL-6 from M Phi. However, when the IL-33 was preincubated with ST2 prior to its addition to the M Phi cultures, the secretion of IL-6 was attenuated. These data suggest that, though IL-33 induced the Th2-type immune responses and infiltration of M2 type M Phi into the peritoneal cavity, ST2 can downregulate these reactions both in vivo and in vitro.
Ohto-Ozaki
Hiromi
H
Department of Biochemistry, School of Medicine, Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi, Japan.
Kuroiwa
Kenji
K
Mato
Naoko
N
Matsuyama
Yasushi
Y
Hayakawa
Morisada
M
Tamemoto
Hiroyuki
H
Tominaga
Shin-ichi
S
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007378:Interleukins / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013163:Splenomegaly / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology
C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D018123:Receptors, Interleukin