Regulation of pro-inflammatory cytokine and Type I,II interferon expression in poly I:C treated Human OAS3-deficient HT1080 cells
Year: 2017
Type: dissertation
Abstract: The mammalian innate immune system uses several sensors of double-stranded RNA(dsRNA) to develop the interferon response. Among these sensors, the 2',5'-oligoadenylate synthetases (OAS) produce 2',5'-linked RNA molecules (2-5A) that accelerate RNA degradation in mammalian tissues. In humans, the OAS family consists of four members: OAS1, OAS2, OAS3, and OASL. OAS1, OAS2, OAS3 have 2',5'-oligoadenylate synthetase activity, whereas OASL has no this activity despite sharing significant sequence similarity with the other OAS proteins. Mainly previous papers focused on the correlation between OAS1 and antiviral effect, however, correct roles of OAS3 are unknown. Here, we generated the OAS3 knockout cells through CRISPR-CAS9 to examine the antiviral function of human OAS3. We found that expression of pro-inflammatory cytokines, Type �뀪,�뀫 interferon was significantly reduced in poly I:C treated OAS3 deficient cell and RNA degradation decreases upon activation of TLR3 signaling by intra-cellular poly I:C transfection in OAS3 knockout cells. In detail, those results provide a severe reduction in IFN-棺,款, IL-6 and TNF induction during stimulation by poly I:C. In contrast, IL-1棺 induction is enhanced by poly I:C. Taken together, these results indicated human OAS3 modulates expression of IFN-棺 involved in Type�뀪 interferon, IFN-款 related to Type�뀫 interferon, IL-6 and TNF engaged in pro-inflammatory cytokine and RNA degradation. \n \n \n�룷�쑀�룞臾쇱쓽 �꽑泥쒖꽦 硫댁뿭 �떆�뒪�뀥�� �씤�꽣�럹濡� 諛섏쓳�쓣 �뼢�긽�븯湲� �쐞�빐 �몢 媛��떏 RNA�뿉 ���븳 �뿬�윭 媛�吏� 媛먯떆�옄瑜� �궗�슜�븳�떎. �씠 媛먯떆�옄 以묒뿉 2`,5`-oligoadenylate synthetases (OAS)�뒗 �룷�쑀�룞臾쇱쓽 議곗쭅�뿉�꽌 RNA 遺꾪빐瑜� 珥됱쭊�븯�뒗 2`,5`-linked RNA molecules (2-5A)瑜� �깮�궛�븳�떎. �궗�엺�뿉�꽌 OAS family�뒗 OAS1, OAS2, OAS3, OASL �꽕 醫낅쪟濡� 援ъ꽦�맂�떎. OAS1, OAS2, OAS3�뒗 2`,5`-oligoadenylate synthetase �솢�꽦�쓣 媛�吏�吏�留�, OASL�� �씠 �솢�꽦�쓣 媛�吏�吏� �븡�뒗�떎. 洹몃윴�뜲�룄 �떎瑜� OAS �떒諛깆쭏�뱾怨� �꽌�뿴�쓽 �쑀�궗�꽦�쓣 留롮씠 媛�吏�怨� �엳�떎. 二쇰줈 �씠�쟾 �끉臾몃뱾�뿉�꽌�뒗 OAS1 怨� �빆諛붿씠�윭�뒪 �슚怨쇱쓽 �긽�샇 �뿰愿��꽦�뿉 ���빐 以묒젏�쓣 �몢怨� �엳�뿀怨�, OAS3�쓽 �뿭�븷�뿉 ���빐�꽌�뒗 �옒 �븣�젮吏�吏� �븡�븯�떎. �뿬湲�, �슦由щ뒗 �궗�엺 OAS3�쓽 �빆諛붿씠�윭�뒪 湲곕뒫�쓣 議곗궗�븯湲� �쐞�빐 CRISPR-CAS9�쓣 �씠�슜�븯�뿬 OAS3媛� 寃곗뿬�맂 �꽭�룷瑜� 留뚮뱾�뿀�떎. �슦由щ뒗 OAS3媛� 寃곗뿬�맂 �꽭�룷�뿉�꽌 �쟾�뿼利앹꽦 �궗�씠�넗�궓怨� ���엯 �뀪,�뀫 �씤�꽣�럹濡좎쓽 諛쒗쁽�웾�씠 �쁽���엳 以꾩뼱�뱶�뒗 寃껉낵 �꽭�룷 �궡遺�濡� poly I:C瑜� �삎吏덉＜�엯�떆耳� TLR3瑜� �솢�꽦�솕�뻽�쓣 �븣 RNA 遺꾪빐�룄 媛먯냼�븯�뒗 寃껋쓣 諛쒓껄�뻽�떎. �옄�꽭�엳 留먰븯硫�, 洹� 寃곌낵�뒗 poly I:C �옄洹뱀뿉 ���빐 IFN-棺, IFN-款, IL-6, TNF �쓽 諛쒗쁽�씠 湲됯꺽�엳 以꾩뼱�뱺 寃껋쓣 蹂댁뿬以��떎. 諛섎�濡� IL-1棺�쓽 諛쒗쁽�� poly I:C �옄洹� �븣臾몄뿉 �뒛�뼱�궃�떎. �넻���뼱 遊ㅼ쓣 �븣, �씠 寃곌낵�뱾�� �궗�엺 OAS3媛� ���엯�뀪�씤�꽣�럹濡좎씤 IFN-棺, ���엯�뀫 �씤�꽣�럹濡좎씤 IFN-款, �쟾�뿼利앹꽦 �궗�씠�넗移댁씤�씤 IL-6, TNF�쓽 諛쒗쁽怨� RNA 遺꾪빐瑜� 議곗젅�븿�쓣 �꽕紐낇빐 以��떎.
Author: 이동현
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2940820374