國家衛生研究院 NHRI:Item 3990099045/7431
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    題名: CCAAT/enhancer binding protein delta in Macrophages Contributes to Immunosuppression and Inhibits Phagocytosis in Nasopharyngeal Carcinoma
    作者: Hsiao, YW;Li, CF;Chi, JY;Tseng, JT;Chang, Y;Hsu, LJ;Lee, CH;Chang, TH;Wang, SM;Wang, DD;Cheng, HC;Wang, JM
    貢獻者: Division of Infectious Diseases
    摘要: Although tumors tend to be associated with immune cells and inflammation, this immune response often fails to eliminate the cancer and instead promotes cancer progression. Tumor-associated macrophages (TAMs) fail to phagocytose tumor cells, and they also produce signals that suppress the adaptive immune response. We showed that immunosuppressive prostaglandin E2 (PGE2) led to the production and activity of the transcription factor CCAAT/enhancer binding protein delta (C/EBPdelta) by stimulating the nucleocytoplasmic shuttling of the RNA binding protein Hu antigen R (HuR), which bound to and stabilized CEBPD mRNA in macrophages. An increase in C/EBPdelta abundance in macrophages in response to PGE2 resulted in enhanced production of the immunosuppressive cytokine interleukin-10 (IL-10) and of pentraxin 3 (PTX3), which suppresses the ability of macrophages to phagocytose tumor cells. Furthermore, conditioned medium from C/EBPdelta-replete, but not C/EBPdelta-deficient, macrophages inhibited the phagocytosis of tumor cells by macrophages, suggesting an autocrine mode of regulation. Immunohistochemical analysis demonstrated that the amount of cytosolic HuR protein correlated with increased C/EBPdelta abundance in TAMs in malignant nasopharyngeal carcinoma. Together, these data suggest that the inflammatory PGE2-HuR-C/EBPdelta axis in macrophages promotes tumor progression by preventing the phagocytosis of tumor cells and inducing immunosuppressive cytokine production.
    日期: 2013-07-16
    關聯: Science Signaling. 2013 Jul 16;6(284):Article number ra59.
    Link to: http://dx.doi.org/10.1126/scisignal.2003648
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1945-0877&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000321829600002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84880868221
    顯示於類別:[張堯] 期刊論文

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