SBi4211阻断HIV-1 gp41促进新生隐球菌对人脑微血管内皮细胞的黏附作用  

HIV-1 gp41-enhanced binding of Cryptococcus neoformans to human brain microvascular endothelial cells is blocked by SBi4211

作　　者：魏轶 彭亮[2,3] 李莉 何肖龙 吴学东[3,5] 曾志节 杨伟军 曹虹[1] 黄胜和 WEI Yi;PENG Liang;LI Li;HE Xiao-Long;WU Xue-Dong;ZENG Zhi-Jie;YANG Wei-Jun;CAO Hong;HUANG Sheng-He(Department of Microbiology,Guangdong Provincial Key Laboratory of Tropical Diseases Research,School of Public Health,Southern Medical University,Guangzhou,Guangdong 510515,China;Department of Clinical Laboratory,The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou,Guangdong 510700, China;Saban Research Institute,Children's Hospital Los Angeles,University of Southern California,Los Angeles 90027,America;Kunming Key Laboratory of Children Infection and Immunity,Yunnan Institute of Pediatrics,Kunming Children's Hospital,Kunming,Yunnan 650228, China;Department of Pediatrics,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China)

机构地区：[1]南方医科大学公共卫生学院广东省热带病研究重点实验室微生物学系,广东广州510515 [2]广州医科大学附属第五医院检验科,广东广州510700 [3]Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles 90027, America [4]昆明市儿童医院云南省儿科研究所昆明市儿童感染与免疫重点实验室,云南昆明650228 [5]南方医科大学南方医院儿科系,广东广州510515

出　　处：《微生物学通报》2019年第6期1496-1501,共6页Microbiology China

基　　金：国家自然科学基金(81370740);广东省自然科学基金重点项目(2017B030311017);中国博士后科学基金(2018M633076)~~

摘　　要：【背景】目前艾滋病和新型隐球菌性脑膜炎共病因素导致其高发病率和死亡率的机制尚不明确。【目的】探索S100B抑制剂SBi4211对HIV-1 gp41促进新生隐球菌黏附人脑微血管内皮细胞的影响和可能机制。【方法】黏附实验分析SBi4211是否能阻断HIV-1 gp41诱导下新生隐球菌黏附人脑微血管内皮细胞。使用免疫印迹方法进一步检测在此过程中SBi4211对脑微血管内皮细胞上新生隐球菌透明质酸受体CD44表达的影响。【结果】SBi4211可显著抑制HIV-1gp41对新生隐球菌黏附脑微血管内皮细胞的增强作用,且呈时间、剂量效应(P<0.05);免疫印迹结果显示SBi4211可抑制新生隐球菌和/或HIV-1 gp41增加脑微血管内皮细胞上新生隐球菌透明质酸受体CD44的表达。【结论】SBi4211可通过下调受体CD44来阻断HIV-1 gp41对新生隐球菌黏附人脑微血管内皮细胞的增强效应,这为了解HIV-1与新生隐球菌共病机制及其防治策略提供了新思路。[Background] The prevalence of neuroAIDS and Cryptococcus neoformans meningitis has significantly increased and the mechanism remains unclear.[Objective] To study the inhibitory effect of SBi4211 on adhesion of C. neoformans to human brain microvascular endothelial cells(HBMEC) induced by HIV-1 gp41.[Methods] The adhesion experiments were carried out to determine whether SBi4211 could block C. neoformans adhesion. Furthermore, the expression of hyaluronic acid CD44 was analyzed by the Western Blot method(WB) during the adhesion process.[Results] SBi4211 could significantly inhibit the HIV-1 gp41-enhanced adhesion of C. neoformans to HBMEC in a dose-and time-dependent manner(P<0.05).Meanwhile expression of the C. neoformans hyaluronic acid receptor CD44 on HBMEC is down regulated.[Conclusion] Our study suggested SBi4211 could block HIV-1 gp41-enhanced adhesion of C. neoformans to HBMEC by reducing expression of receptor CD44, which might provide novel insights into understanding the mechanisms of C. neoformans and HIV-1 associated comorbidity besides its prevention and treatment.

关 键 词：新生隐球菌 S100B抑制剂 HIV-1 GP41 CD44 人脑微血管内皮细胞 

分 类 号：R379.5[医药卫生—病原生物学]