铁杉灵芝多糖FⅢ-2对人组织瘤细胞和人外周血白细胞产生炎症性细胞因子的影响(英文)

Effect of polysaccharide FⅢ-2 from Ganoderma tsugae on proinflammatory cytokine production by THP-1 cells and human peripheral blood mononuclear cells

用放射免疫分析法及逆转录聚合酶链反应法 ,比较研究水不溶性铁杉灵芝多糖 (FⅢ 2 )及其吡啶 氯磺酸修饰产物 (FⅢ 2 S)对人炎症性细胞因子蛋白质及其mRNA产生的影响 .结果表明 ,FⅢ 2 (4 ,4 0或 4 0 0mg·L- 1)显著提高低剂量脂多糖 (LPS) 10mg·L- 1协同佛波醇 14烷酰乙酸盐 (PMA) 2 0 0nmo1·L- 1诱导的人组织瘤THP 1细胞产生肿瘤坏死因子α(TNFα) ,然而明显地抑制高剂量LPSl0 0mg·L- 1协同PMA诱导的THP 1细胞产生TNFα .FⅢ 2 S(4或4 0mg·L- 1)提高无刺激剂细胞产生TNFα ,高浓度FⅢ 2 S(4 0 0mg·L- 1)抑制TNFα产生 .FⅢ 2与FⅢ 2 S提高白介素 8的产生 ,降低刺激剂引起的白介素 1α的产生 .FⅢ 2的抗肿瘤作用可能是与TNFα产生有关 .FⅢ 2对人外周血单核细胞产生各种细胞因子和对THP 1细胞产生细胞因子的机理基本上相同 .结果提示 ,松杉灵芝菌丝体水不溶性多糖在不同的刺激条件下具有双向免疫调节作用 .化学修饰的多糖可改变原多糖对细胞因子产生的调节方向 .

Regulatory effects of water insoluble polysaccharide FⅢ 2 (FⅢ 2) and its pyridine chlorosulfonic acid modified water soluble polysaccharide FⅢ 2 S (FⅢ 2 S) on the production of proinflammatory cytokines were investigated. FⅢ 2 and FⅢ 2 S down regulated IL 1α production by THP 1 cells stimulated by higher concentration of lipopolysaccharide (LPS) and phorbol myristate acetate (PMA), whereas they up regulated IL 8 secretion without stimulants or at weaker stimulatory conditions. FⅢ 2 itself induced TNFα production by THP 1 cells and at relatively weak stimulatory conditions with LPS 10 mg·L -1 and PMA 200 nmol·L -1 significantly up regulated TNFα production in a dose dependent manner. However, at higher concentration of LPS (100 mg·L -1 ) and PMA (200 nmol·L -1 ), FⅢ 2 down regulated TNFα production of stimulated THP 1. Human peripheral blood mononuclear cells (PMBC) responded to FⅢ 2 and FⅢ 2 S in IL 1α, IL 8 and TNFα production in a fashion similar to THP 1 cell responses. FⅢ 2 and FⅢ 2 S regulated mRNA expression for IL 1α and TNFα. Production of TNFα protein reflected quantity of TNFα mRNA, however, IL 1α mRNA expression did not coincide with IL 1α protein production. In conclusion, the polysaccharides of Ganoderma tsugae mycelium have immunomodulatoryeffects on the production of proinflammatory cytokines. Chemical modification changes the intensity and reverses the direction of regulatory effects of the polysaccharides on proinflammatory cytokine production.