title: Apolipoprotein A-II suppressed concanavalin A-induced hepatitis via the inhibition of CD4 T cell function.
abstract: Con A-induced hepatitis has been used as a model of human autoimmune or viral hepatitis. During the process of identifying immunologically bioactive proteins in human plasma, we found that apolipoprotein A-II (ApoA-II), the second major apolipoprotein of high-density lipoprotein, inhibited the production of IFN-γ by Con A-stimulated mouse and human CD4 T cells. Con A-induced hepatitis was attenuated by the administration of ApoA-II. The beneficial effect of ApoA-II was associated with reduced leukocyte infiltration and decreased production of T cell-related cytokines and chemokines in the liver. ApoA-II inhibited the Con A-induced activation of ERK-MAPK and nuclear translocation of NFAT in CD4 T cells. Interestingly, exacerbated hepatitis was observed in ApoA-II-deficient mice, indicating that ApoA-II plays a suppressive role in Con A-induced hepatitis under physiological conditions. Moreover, the administration of ApoA-II after the onset of Con A-induced hepatitis was sufficient to suppress disease. Thus, the therapeutic effect of ApoA-II could be useful for patients with CD4 T cell-related autoimmune and viral hepatitis.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamashita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Kaori
authors.initials: K
authors.lastname: Hada
authors.forename: Naoko
authors.initials: N
authors.lastname: Hara
authors.forename: Munehisa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kaneshiro
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kaneko
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003208:Concanavalin A / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D055786:Gene Knockout Techniques; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
chemical_list: C115794:APOA2 protein, human; D016633:Apolipoprotein A-II; D006131:Growth Inhibitors; D003208:Concanavalin A; D007371:Interferon-gamma