G1-4A, an immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock
G1-4A, an immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock
复制标题
DOI：
10.1016/j.intimp.2007.06.004
复制
发表时间：
2007-10-01
影响因子：
5.6
通讯作者：
Sainis, K. B.
中科院分区：
文献类型：
--
作者：
Desai, Veena R.;Ramkrishnan, Rupal;Sainis, K. B.
促炎细胞因子是内毒素休克的介质，一些免疫调节中药可以调节这些细胞因子的表达。因此，我们已经研究了使用来自青牛胆茎的阿拉伯半乳聚糖多糖G1 -4A用于对抗内毒素诱导的脓毒症的可能性。在用G1 -4A预处理的小鼠中存在针对脂多糖（LPS）诱导的死亡的100%保护。为了阐明作用机制，评价了其对巨噬细胞（这些促炎分子的主要来源）的影响。显示G1 -4A结合鼠巨噬细胞，导致其活化，并且LPS与巨噬细胞的结合受到抑制。在用G1 -4A治疗后，血清TNF-α和IL-1 β水平略有增加。然而，与对照相比，用LPS攻击引起G1 -4A预处理的小鼠中TNF-α水平显著降低，而可溶性TNFR水平提高。与对照相比，在用G1 -4A预处理的小鼠中，在用LPS攻击后观察到血清IL-1 β、IL-6、IFN-γ水平的增加和IL-10水平的降低。此外，G1 -4A还调节小鼠巨噬细胞释放一氧化氮。在人单核细胞系U937中观察到类似的现象。因此，G1 -4A似乎通过调节细胞因子和一氧化氮诱导对内毒素休克的耐受。(c)2007 Elsevier B. V.保留所有权利。
Pro-inflammatory cytokines are known to be the mediators of endotoxic shock and several immunomodulatory herbs can modulate the expression of these cytokines. Therefore we have investigated the possibility of using an arabinogalactan polysaccharide, Gl-4A, from the stem of Tinospora cordifolia, for protection against endotoxin induced sepsis. There was 100% protection against lipopolysaccharide (LPS) induced mortality in mice pretreated with Gl-4A. To elucidate the mechanism of action, its effect on macrophages, the primary source of these pro-inflammatory molecules was evaluated. G l-4A was shown to bind to the murine macrophages leading to their activation and reciprocally inhibited binding of LPS to macrophages. Following treatment with Gl-4A, there was a small increase in serum TNF-alpha and IL-l beta levels. However, challenge with LPS elicited significantly reduced levels of TNF-a in G l-4A pretreated mice as compared to the controls while the level of soluble TNFR was enhanced. An increase in serum IL-l beta, IL-6, IFN-gamma levels and decrease in that of IL-10 was observed following challenge with LPS in mice pretreated with Gl-4A as compared to the controls. In addition, Gl-4A also modulated the release of nitric oxide by murine macrophages. Similar phenomenon was observed in a human monocytic cell line, U937. Thus Gl-4A appeared to induce tolerance against endotoxic shock by modulation of cytokines and nitric oxide. (c) 2007 Elsevier B.V. All rights reserved.