Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Immunology / 免疫學研究所
  4. The role of STAT3 inhibitors in Type I IFN-mediated signaling and antiviral responses
 
  • Details

The role of STAT3 inhibitors in Type I IFN-mediated signaling and antiviral responses

Date Issued
2012
Date
2012
Author(s)
Liao, Chien-Hui
URI
http://ntur.lib.ntu.edu.tw//handle/246246/248015
Abstract
Type I interferons (IFNs) plays a key role in innate immunity to protect host from viral and bacterial infections. Signal transducer and activator of transcription (STAT) proteins, such as STAT1, STAT2, and STAT3, are activated by IFN-α/β. Unlike the complex of STAT1 and STAT2, which promotes type I IFN-mediated antiviral response, STAT3 negatively regulates type I IFN-mediated pathway. In previous study, STAT3 knockout mouse fibroblast (MEFs) and primary bone-marrow-derived macrophages (BMMs) showed enhanced IFN functions. We hypothesize that targeting STAT3 function would enhance IFN-mediated antiviral response. Therefore, we screened different STAT3 inhibitors and investigated their roles in IFN-mediated signaling and functions. Among them, WP1066 was shown to induce higher expression of antivirus-associated genes in both WT MEFs and BMMs in response to IFN-α4 stimulation. Interestingly, the phenomenon was abolished in the absence of STAT3, suggesting that the effect of the inhibitor was STAT3-dependent. The effect of WP1066 in IFN-α4-mediated antiviral response was further examined by infecting MEFs with encephalomyocarditis virus (EMCV). Enhanced antiviral response was revealed by reduced expression of EMCV-specific gene in infected cells in a dose-dependent manner. In addition, the suppressive effect of FL- and N-terminal domain- (NTD) STAT3 in STAT3KO MEFs in response to type I IFN was reversed by WP1066 treatment. We further addressed the mechanism of WP1066 activity and found that the inhibitor did not affect phosphorylation and nuclear translation of STAT1 and STAT2. Taken together, these results suggest that WP1066 may enhance antiviral function of cells by targeting STAT3 function. This study provides a therapeutic approach for virus infection by targeting STAT3 to enhance type I IFN-induced antiviral response.
Subjects
STAT3
inhibitor
interferon
Type
thesis
File(s)
Loading...
Thumbnail Image
Name

ntu-101-R99449001-1.pdf

Size

23.32 KB

Format

Adobe PDF

Checksum

(MD5):f1c29a99577ebda78337eb2fd54c37d0

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science