Soluble branched β-(1,4)Glucans from Acetobacter species show strong activities to induce interleukin-12 in vitro and inhibit T-helper 2 cellular response with immunoglobulin E production in vivo

Soluble branched β-(1,4)Glucans from Acetobacter species show strong activities to induce interleukin-12 in vitro and inhibit T-helper 2 cellular response with immunoglobulin E production in vivo
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DOI:
10.1074/jbc.m304948200
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发表时间:
2003-10-03
影响因子:
4.8
通讯作者:
Yoshikai, Y
Yoshikai, Y
中科院分区:
生物学2区
文献类型:
--
作者:
Saito, K;Yajima, T;Yoshikai, Y

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由产多糖醋杆菌(Acetobacter polysaccharogenes)产生的胞外多糖AC-1由具有葡糖基残基支链的β-(1,4)葡聚糖组成。我们发现,AC-1显示出强烈的活性,诱导产生白细胞介素-12 p40和肿瘤坏死因子-α的巨噬细胞系在体外。纤维素酶处理完全消除AC-1诱导巨噬细胞产生肿瘤坏死因子-α的活性,而用多粘菌素B或蛋白酶处理AC-1不影响活性。使用Toll样受体(TLR)4缺陷小鼠和TLR 4转染的人细胞系的实验结果表明,TLR 4参与AC-1的模式识别。在用OVA免疫的小鼠中,AC-1的体内给药显著降低了卵清蛋白(OVA)特异性IgE的血清水平和响应于OVA的T细胞产生的白细胞介素-4。AC-1是一种可溶性支链β-(1,4)葡聚糖,可用于预防和治疗伴随IgE产生的过敏性疾病。
An extracellular polysaccharide, AC-1, produced by Acetobacter polysaccharogenes is composed of beta-(1,4) glucan with branches of glucosyl residues. We found that AC-1 showed a strong activity to induce production of interleukin-12 p40 and tumor necrosis factor-alpha by macrophage cell lines in vitro. Cellulase treatment completely abolished the activity of AC-1 to induce tumor necrosis factor-alpha production by macrophages, whereas treatment of AC-1 with polymyxin B or proteinase did not affect the activity. Results of experiments using Toll-like receptor (TLR) 4-deficient mice and TLR4-transfected human cell line indicated that TLR4 is involved in pattern recognition of AC-1. In vivo administration of AC-1 significantly reduced the serum levels of ovalbumin (OVA)-specific IgE and interleukin- 4 production by T cells in response to OVA in mice immunized with OVA. AC-1, a soluble branched beta-(1,4) glucan may be useful in prevention and treatment of allergic disorders with IgE production.