Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes
Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes
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DOI：
10.1152/ajpgi.00105.2005
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发表时间：
2005-11-01
影响因子：
4.5
通讯作者：
Ilan, Y
中科院分区：
文献类型：
--
作者：
Margalit, M;Abu Ghazala, S;Ilan, Y
刀豆蛋白A （ConA）诱导自然杀伤T （NKT）细胞介导的肝损伤。糖脑苷（GC）是一种天然存在的糖脂。我们的目的是确定GC在cona诱导的小鼠肝炎模型中的作用。A组和B组小鼠分别在ConA给药前2h和给药后2h给予GC；C组小鼠给予ConA；D组小鼠灌胃GC；E组小鼠不接受任何治疗。采用血清谷草转氨酶（AST）、丙氨酸转氨酶（ALT）水平及肝脏组织学指标评价肝损害程度。GC的免疫作用通过肝内和脾内NKT淋巴细胞的荧光活化细胞分选分析、细胞因子水平测定和STAT 1、4、6和NF-kappa B表达的Western blot分析来确定。体外观察GC对NKT细胞增殖的影响。与未处理的C组相比，GC处理的A组小鼠血清AST和ALT水平明显降低，组织损伤明显减轻。GC的有益作用与肝内NKT淋巴细胞减少20%，血清ifn - γ水平显著降低，STAT1和STAT6表达降低有关。体外给药GC导致树突状细胞存在时NKT细胞增殖减少42%，而树突状细胞不存在时则没有。腹腔注射放射性GC在肝脏和肠道中被检测到。GC的管理导致ConA肝炎的改善与NKT淋巴细胞抑制作用相关。GC有望成为一种新的免疫调节剂。
Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intra-splenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-kappa B expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.