Department of Dermatology, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
J Investig Allergol Clin Immunol. 2012;22(3):180-7.
Immunoglobulin (Ig) E plays an important role in the pathogenesis of allergic diseases such as atopic dermatitis and allergic asthma.We previously reported that a sulfate polysaccharide, fucoidan, suppressed IgE production by murine B cells in vitro. However, the mechanism by which fucoidan suppresses IgE production remains unclear.
We incorporated sulfate groups into cellulose and studied their biological characteristics in vitro to explore the possibility of converting biologically neutral polysaccharides to active reagents with antiallergic functions.
Cellulose was chemically processed using N,N-dimethylformamide (DMF) and DMF-sulfurtrioxide and recovered as cellulose sulfate with a molecular weight of around 10 kDa. We then studied the effect of cellulose sulfate on IgE production from B cells, IgE class-switching, and populations of IgE-secreting B cells prepared from murine spleen. We also investigated the effects of sulfated cellulose on the production of interleukin (IL) 4 and interferon (IFN) gamma and the expression of T-bet mRNA by splenic T cells. The cytotoxicity of cellulose sulfate was also examined.
Cellulose sulfate suppressed IgE production in B cells stimulated with IL-4 and anti-CD40 antibody by inhibiting IgE class-switch recombination and decreasing the number of IgE-secreting B cells in vitro. Moreover, both cellulose sulfate and fucoidan suppressed IL-4 production and enhanced IFN-gamma production by murine T cells stimulated with anti-CD3 and anti-CD28 antibodies, despite the decrease in T-bet mRNA expression.
Cellulose gains an antiallergic effect on B cells and T cells with the addition of sulfate groups.
免疫球蛋白 E(IgE)在特应性皮炎和过敏性哮喘等过敏性疾病的发病机制中起着重要作用。我们之前报道过,硫酸多糖岩藻聚糖通过体外抑制小鼠 B 细胞 IgE 的产生。然而,岩藻聚糖抑制 IgE 产生的机制尚不清楚。
我们将硫酸基团引入纤维素中,并研究其体外的生物学特性,以探索将生物学上中性的多糖转化为具有抗过敏功能的活性试剂的可能性。
使用 N,N-二甲基甲酰胺(DMF)和 DMF-三氧化硫对纤维素进行化学处理,并回收分子量约为 10 kDa 的纤维素硫酸盐。然后,我们研究了纤维素硫酸盐对 B 细胞 IgE 产生、IgE 类别转换以及从鼠脾制备的 IgE 分泌 B 细胞群体的影响。我们还研究了硫酸化纤维素对白细胞介素(IL)4 和干扰素(IFN)γ产生以及脾 T 细胞 T-bet mRNA 表达的影响。还检查了纤维素硫酸盐的细胞毒性。
纤维素硫酸盐通过抑制 IgE 类别转换和减少体外刺激的 B 细胞中 IgE 分泌 B 细胞的数量来抑制由 IL-4 和抗 CD40 抗体刺激的 B 细胞中 IgE 的产生。此外,纤维素硫酸盐和岩藻聚糖均抑制由抗 CD3 和抗 CD28 抗体刺激的鼠 T 细胞中 IL-4 的产生并增强 IFN-γ的产生,尽管 T-bet mRNA 表达减少。
通过添加硫酸基团,纤维素对 B 细胞和 T 细胞具有抗过敏作用。