PP2A抑制剂LB-100通过促进TNF-α和IL-6产生治疗白念珠菌感染  

PP2A inhibitor LB-100 alleviates Candida albicans infection through promoting production of TNF-α and IL-6

作　　者：郭文 王中伟 吴梦雪 贾鑫明[1] GUO Wen;WANG Zhongwei;WU Mengxue;JIA Xinming(School of Medicine,Tongji University,Shanghai 200092,China)

机构地区：[1]同济大学医学院,上海200092

出　　处：《同济大学学报（医学版）》2022年第6期769-775,共7页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金(81901673)。

摘　　要：目的 探讨LB-100在小鼠念珠菌病模型中的作用。方法 尾静脉注射构建小鼠念珠菌病模型,LB-100腹腔给药,监测并记录小鼠生存率。感染48 h后摘取肾脏和肝脏统计荷菌量。分别用灭活的白念珠菌酵母态和菌丝态以及白念珠菌来源的α-mannan和β-glucan刺激小鼠骨髓来源的巨噬细胞(bone marrow derived macrophages, BMDMs),ELISA检测上清液中TNF-α和IL-6水平,qPCR检测TNF-α和IL-6 mRNA的表达及稳定性,Western印迹法检测p38丝裂原活化蛋白激酶的磷酸化水平和三四脯氨酸(TTP)的表达。结果 体内试验表明,与未治疗组相比,LB-100治疗白念珠菌感染小鼠的存活时间显著延长(P<0.05),同时各脏器荷菌量显著降低(P<0.05)。体外结果显示,LB-100处理后,BMDMs中TNF-α和IL-6的表达显著上升,其mRNA的表达及稳定性显著增强(P<0.05)。结论 LB-100能够改善白念珠菌引起的念珠菌病,为临床抗念珠菌病治疗提供新的思路。Objective To investigate the role of LB-100 in alleviation of Candida albicans infection in mice. Methods A mouse model of candidiasis was established by tail vein injection of Candida albicans, and LB-100 was administered intraperitoneally. Survival of mice was monitored. After 48 h of infection, animals were sacrificed, kidney and liver samples were collected and fungal burden was analyzed. Bone marrow-derived macrophages(BMDMs) were stimulated with inactivated C.albicans yeast cells and hyphae, and C.albicans-derived α-mannan and β-glucan, respectively. The levels of TNF-α and IL-6 in the culture supernatant were detected by ELISA, the expression and stability of TNF-α and IL-6 mRNA were detected by qPCR, the phosphorylation level of p38 MAPK and the expression of tristetraprolin(TTP) were detected by Western blotting. Results Compared with control group, LB-100 treatment significantly prolonged the survival in infected group(P<0.05), and at the same time, the fungal burden in kidney and liver was significantly reduced(P<0.05). In vitro results showed that after LB-100 treatment, the expressions of TNF-α and IL-6 in BMDMs were significantly increased, and the expression and stability of their mRNAs were significantly enhanced(P<0.05). Conclusion LB-100 treatment can alleviate candidiasis caused by C.albicans in mice through promoting TNF-α and IL-6 production.

关 键 词：念珠菌病 蛋白磷酸酶2A LB-100 小鼠 

分 类 号：R392[医药卫生—免疫学]