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《Current Immunology》 2014-01
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THP-1 activates signal pathway of TLR in ovarian cancer cell line SKOV3

XU Juan;PAN Shi-yang;LOU Jian-fang;SHI Xin-hui;HUANG Pei-jun;ZHANG shu-ping;KE Xing;ZHU Sheng-jiang;SUN Rui-hong;HUANG Lei;WANG Fang;Department of Laboratory Medicine,the First Affiliated Hospital of Nanjing Medical University;Key Laboratory for Laboratory Medicine of Jiangsu Province;  
Ovarian cancer has a disproportionately high mortality rate.It is well known that Toll like receptors(TLRs) play an important role in tissue repairing,inflammation and tumour progression.As TLRs in the monocyte are thought to play a key role in promoting tumor growth through inflammation-dependent mechanism,THP-1,SK-OV-3 co-culture system and antiTLR1,anti-TLR2,anti-TLR6 mAb blocking experiment were used to explore the relationship between TLR1,TLR2 or TLR6signaling and inflammation in ovarian cancer.Quantitative real-time PCR was used to measure IL-1β,IL-6,IL-8,and TNF-a in the periphral mononuclear cells(PBMC).MyD88,TRAF6,TANK,NF-kB and P-NFkB were observed by Western blot.In the THP-1 and SK-OV-3 coculture system,we found the activation of TLRs signaling pathways,including significantly increased MyD88,TRAF6,TANK and P-NF-kB levels in THP-1 following cocultured with SK-OV-3.THP-1 led to an increase in IL-1β,IL-8 and TNF-α mRNA levels after 24 hours of co-incubation with SK-OV-3(Fold=4.27,Fold = 4.92,Fold=3.08,P0.05),though there was no difference of IL-6 mRNA expression.THP-1 when treated with anti-TLRl,anti-TLR2 or-TLR6 mAbs could inhibit production of inflammatory cytokines IL-10(Fold=0.43,Fold=0.38,Fold=0.44,P0.05),IL-8(Fold=0.43,Fold = 0.48,Fold=0.42,P0.05) and TNF-α(Fold = 0.23,Fold = 0.21,Fold=0.23,P0.05) and activation of MyD88,TRAF6,TANK,NF-kB and P-NF-kB.These results support the idea that the presence of factors in the tumor microenvironment can act through TLRs signaling to induce increased expression of IL-1|3,IL-8,TNF-a and MyD88,TRAF6,TANK,P-NF-kB in THP-1.TLR1/TLR2/TLR6 in THP-1 participate in the recognition of the tumor microenvironment factors.By activating TLR1/TLR2/TLR6,the expression levels of inflammatory cytokines IL-lfi,IL-6,TNF-a and TLR signaling molecules MyD88,TRAF6,TANK,NF-kB,P-NF-kB were up-regulated.
【Fund】: 国家自然科学基金(30901344;81272324);; 江苏省实验诊断学重点实验室基金(XK 201114)
【CateGory Index】: R737.31
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【Co-citations】
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【Secondary Citations】
Chinese Journal Full-text Database 1 Hits
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