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IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling
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  • IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling
  • IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling
저자명
Xiong. Hai-Yu,Ma. Ting-Ting,Wu. Bi-Tao,Lin. Yan,Tu. Zhi-Guang
간행물명
Asian Pacific journal of cancer prevention : APJCP
권/호정보
2014년|15권 14호|pp.5767-5772 (6 pages)
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아시아태평양암예방학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${gamma}$ and further activating the NF-${kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${gamma}$ and inhibition of expression of IL-10.