Apolipoprotein A-II Suppressed Concanavalin A-Induced Hepatitis via the Inhibition of CD4 T Cell Function

作者：Yamashita Junji; Iwamura Chiaki; Sasaki Tetsuya; Mitsumori Kunitoshi; Ohshima Kazutoshi; Hada Kaori; Hara Naoko; Takahashi Munehisa; Kaneshiro Yoshiaki; Tanaka Hitoshi; Kaneko Kenji; Nakayama Toshinori^*

来源：The Journal of Immunology, 2011, 186(6): 3410-3420.

DOI：10.4049/jimmunol.1002924

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-gamma 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. The Journal of Immunology, 2011, 186: 3410-3420.

• 出版日期2011-3-15