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

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-1 gp41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。

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

Abstract:

[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] SBi4211could 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.

Key words:C. neoformans, S100B inhibitor, HIV-1 gp41, CD44, Human brain microvascular endothelial cells