Protective effects of alpha1-acid glycoprotein and serum amyloid A on concanavalin A-induced liver failure via interleukin-6 induction by ME3738.
We examined whether the 22beta-methoxyolean-12-ene-3beta,24(4beta)-diol (ME3738)-mediated selective induction of interleukin-6 increased alpha1-acid glycoprotein and serum amyloid A expression, and whether these proteins protected against liver injury in vitro and in vivo. ME3738 treatment in male mice increased gene expression of alpha1-acid glycoprotein subtypes and serum amyloid A 2 genes, and plasma concentration of serum amyloid A. Treatment with alpha1-acid glycoprotein at 5 mg/animal or serum amyloid A at 0.03 and 0.1 mg/animal prior to concanavalin A administration reduced multifocal necrosis in the liver. Treatment with alpha1-acid glycoprotein and serum amyloid A, but not alpha1-antitrypsin, protected Hep G2 cells against cell injury. These results suggest that alpha1-acid glycoprotein and serum amyloid A, increased by ME3738-induced interleukin-6, might protect against concanavalin A-induced liver injury.
Kuzuhara
Hiroyuki
H
Pharmaceutical Research Center, Meiji Seika, Kaisha Ltd., Kouhoku, Yokohama, Japan.
Nakano
Yoshihisa
Y
Yamashita
Nobuyuki
N
Imai
Masako
M
Kawamura
Yuji
Y
Kurosawa
Tohru
T
Nishiyama
Shoji
S
D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D003208:Concanavalin A / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis*; D017093:Liver Failure / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D009961:Orosomucoid / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D015850:Interleukin-6; C477463:ME3738; D009961:Orosomucoid; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D003208:Concanavalin A; D009828:Oleanolic Acid; D016604:Aflatoxin B1