感染引發之發炎與致癌機轉之探討

Regulatory mechanisms of infection-induced inflammation and carcinogenesis

張雅貞(Ya-Jen Chang)

指導教授 ： 陳青周

國立臺灣大學/醫學院/藥理學研究所/博士(2005年)

https://doi.org/10.6342/NTU.2005.00933

摘要

本論文探討急性呼吸道徵候群冠狀病毒(SARS-CoV)感染肺細胞，或幽門螺旋桿菌(Helicobactor pylori)感染胃上皮細胞，引發發炎或致癌基因包括ICAM-1、IL-8、COX-2或cyclin D1表現之訊息傳遞路徑。
IFN-γ在肺上皮細胞NCI-H292磷酸化STAT1的Y701，受PKC和Src kinase 之調控，IFN-γ和TPA均可活化c-Src而磷酸化STAT1之Y701，且增加這兩者之交互作用。IFN-γ可磷酸化JAK1/2和PLC-γ 之tyrosine，後者之作用受AG490 (JAK 抑制劑)抑制，IFN-γ並增加JAK1/2 和PLCγ之交互作用，表示JAK1/2 可調控PLC-γ的活化，此結果結合先前之發現，證實IFN-γ經由JAK1/2活化PLC-γ、PKC、c-Src 和STAT1；AG490可抑制IFN-γ所引發之JAK1/2 和STAT1之交互作用，但是對TPA之此項作用無影響，因此IFN-γ可經由兩種路徑引發ICAM-1之表現，一為JAK1/2 /PLCγ/PKC/c Src/STAT1，另一為JAK1/2直接活化STAT1。
SARS-CoV 棘蛋白可引發肺細胞釋放IL-8。轉殖SARS-CoV 棘蛋白可活化 IL-8 promoter與AP1，對NF-

關鍵字

急性呼吸道徵候群 ； 癌症 ； 感染 ； 訊息傳遞 ； 發炎 ； 幽門桿菌

並列摘要

The mechanism of SARS-CoV or Helicobactor pylori infection-induced inflammation or carcinogenesis was investigated in this study. Several novel signaling pathways were explored in the regulation of ICAM-1, IL-8, COX-2, or cyclin D1 gene expression.
In lung epithelial NCI-H292 cells, the signaling pathway for IFN-

並列關鍵字

inflammation ； cancer ； infection ； SARS ； Helicobacter pylori ； signal transduction

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