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Chinese Journal of Mycology 2016, Vol. 11  Issue (3): 129-134.

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Cryptococcus traversal across the Blood-Brain Barrier though S100A10-dependent activation of urokinase-plasmin system

QIU Tian wen, ZHU Hong-mei, WEN Hai   

  1. PLA Key Laboratory of Fungal Diseases and Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • Received:2016-05-16 Online:2016-06-28 Published:2016-06-28

Abstract:

Objective To find if Cryptococcus traversal across the blood-brain barrier though S100A10-dependent activation of urokinase-plasmin system.Methods ①The mouse brain microvascular endothelial cells bEnd.3 and Cryptococcus neoformans B3501 were co-incubated.Then the expression of S100A10 gene and UPA genewere tested.②Expressionof S100A10 and UPA in S100A10 normal and silent groups of endothelial cellsInfected with lentivirus were also compared.③The abilities of Cryptococcus S100A10 normal and silent groups traversal across the transwell blood-brain barrier model were compared.Urokinase-related activation of plasminogen was tested by the chromogenic substrate assay.Results ①In bEnd.3 incubated with Cryptococcus neoformans B3501,Real-time PCR display high expression of mRNA of S100A10 and UPA;Western-blot show S100A10 protein and UPA protein overexpression.②While S100A10 gene been silenced,S100A10 and UPA expressions were suppressed.③Cryptococcal traversal across the transwell in vitro BBB model in S100A10 silenced group was less than that of controlgroup.The diffences on 8 h,16 h,24 h were especially statistically significant,P<0.05.The activation of urokinase and plasmin was also lower than that of control group.The diffences of plasminogen activation on 8 h,16 h and 24 h in two groups,the diffences of urokinase activation on 16 h and 24 h in two groups,were statistically significant,respectively.Conclusion Cryptococcus traversal across the blood-brain barrier might be though S100A10-dependent activation of urokinase-plasmin system.In the meantime,the S100A10 gene and UPA gene of brain microvascular endothelial cells were highly expressed.

Key words: Cryptococcus neoformans, S100A10, urokinase, plasmin, blood-brain barrier

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