Parasites, Hosts and Diseases

  • 제56권2호
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  • Pages.135-145
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  • 2018
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  • 2982-5164(pISSN)
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  • 1738-0006(eISSN)
대한기생충학·열대의학회 (The Korea Society for Parasitology and Tropical Medicine)
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Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K/Akt or mTOR Signal Pathway

  • Zhou, Wei (Institute of Immunology, Taishan Medical College) ;
  • Quan, Juan-Hua (Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University) ;
  • Gao, Fei-Fei (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Ismail, Hassan Ahmed Hassan Ahmed (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Lee, Young-Ha (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Cha, Guang-Ho (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine)
  • 투고 : 2017.06.20
  • 심사 : 2018.03.20
  • 발행 : 2018.04.30
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초록

Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

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