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http://dx.doi.org/10.7314/APJCP.2014.15.14.5767

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling  

Xiong, Hai-Yu (College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University)
Ma, Ting-Ting (College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University)
Wu, Bi-Tao (College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University)
Lin, Yan (College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University)
Tu, Zhi-Guang (College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.14, 2014 , pp. 5767-5772 More about this Journal
Abstract
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.
Keywords
Ovarian cancer; B7-H1; IL-12; IFN-${\gamma}$; NF-${\kappa}B$ signaling pathway;
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1 Wysocka M, Kubin M, Vieira LQ, et al (1995). Interleukin-12 is required for interferon-$\gamma$ production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol, 25, 672-6.   DOI   ScienceOn
2 Xiong HY, Ma TT, Wang Q, et al (2014). The effects of ovarian cancer cells co-cultured with macrophages on the expression of B7-H1 and its mechanisms. Chinese J Cell Biol, 35, 1760-4.
3 Bever Jr CT, Morgan KD, Whitaker JN (1989). Cathepsin D activity in human peripheral blood mononuclear leukocytes. Inflammation, 13, 309-16.   DOI
4 Bloch O, Crane CA, Kaur R (2013). Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res, 19, 3165-75.   DOI
5 Brown JA, Dorfman DM, Ma FR, et al (2003). Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol, 170, 1257-66.   DOI
6 Cheng F, Kuang WB, Tu ZG, et al (2012). Construction of adenovirus vector containing hIL-12 gene and its effects on the proliferation and TGF-$\beta$ expression of Hep3B cells. Chinese J Immunol, 28, 402-6.
7 Cheng XD, Zhao Z, Ventura E, et al (2007). The PD-1/PD-L pathway is up-regulated during IL-12-induced suppression of EAE mediated by IFN-gamma. J Neuroimmunol, 185, 75-86.   DOI
8 Chen YW, Zhang JB, Guo GN, et al (2009). Induced B7-H1 expression on human renal tubular epithelial cells by the sublytic terminal complement complex C5b-9. Molecular Immunology, 46, 375-83.   DOI
9 Cheshire JL, Baldwin AS, et al (1997). Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappa B alpha degradation and de novo I kappa B beta degradation. Molecular Cellular Biology, 17, 6746-54.
10 Curiel TJ, Wei S, Dong HD, et al (2003). Blockade of B7- H1 improves myeloid dendritic cell-mediated antitumor immunity. Nature Medicine, 9, 562-7.   DOI
11 Deb A, Haque SJ, Mogensen T, et al (2001). RNA-dependent protein kinase PKR is required for activation of NF-kappaB by IFN- gamma in a STAT1-independent pathway. J Immunol, 166, 6170-80.   DOI
12 Dong HD, Chen L (2003). B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med, 81, 281-7.
13 Dong HD, Strome SE, Salomao DR, et al (2002). Tumorassociated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8, 793-800.
14 Dong HD, Zhu GF, Tamada K, et al (1999). B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature Med, 5, 1365-9.   DOI   ScienceOn
15 Eppihimer MJ, Gunn J, Freeman GJ, et al (2002). Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation, 9, 133-45.   DOI
16 Grivennikov SI, Greten FR, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140, 883-99.   DOI   ScienceOn
17 Huang G, Wen QJ, Zhao YL, et al (2013). NF-kB plays a key role in inducing CD274 expression in human monocytes after lipopolysaccharide treatment. PLoS ONE, 8, 61602.   DOI
18 Jain D, Kumar S (2012). Snake venom: a potent anticancer agent. Asian Pacific J Cancer Prev, 13, 4855-60.   과학기술학회마을   DOI   ScienceOn
19 Karakhanova S, Meisel S, Ring S, et al (2010). ERK/p38 MAPkinases and PI3K are involved in the differential regulation of B7-H1 expression in DC subsets. Eur J Immunol, 40, 254-66.
20 Kobayashi M, Fitz L, Ryan M, et al (1989). Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. JEM, 170, 827-45.   DOI   ScienceOn
21 Kondo A, Yamashita T, Tamura H, et al (2010). Interferon-$\gamma$ and tumor necrosis factor-$\alpha$ induce an immunoinhibitory molecule, B7-H1, via nuclear factor-${\kappa}B$ activation in blasts in myelodysplastic syndromes. Blood, 116, 1124-31.   DOI
22 Konishi J, Yamazaki K, Azuma M, et al (2004). B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res, 10, 5094-100.   DOI
23 Kuang DM, Zhao QY, Peng C, et al (2009). Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. Exp Med, 206, 1327-37.   DOI   ScienceOn
24 Lee SJ, Jang BC, Lee SW, et al (2006). Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Letters, 580, 755-62.   DOI
25 Lee SK, Seo SH, Kima BS, et al (2005). IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells. J Dermatol Sci, 40, 95-103.   DOI
26 Luo JL, Kamata H, Karin M (2005). IKK/NF-kappaB signaling: balancing life and death-a new approach to cancer therapy. J Clin Invest, 115, 2625-32.   DOI   ScienceOn
27 Mantovani A, Sica A (2010). Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol, 22, 231-7.   DOI   ScienceOn
28 Ohigashi Y, Sho M, Yamada Y, et al (2005). Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res, 11, 2947-53.   DOI
29 Stern AS, Podlaski FJ, Hulmes JD, et al (1990). Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci USA, 87, 6808-12.   DOI   ScienceOn
30 Strome SE, Dong HD, Tamura H, et al (2003). B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res, 63, 6501-5.
31 Tjiu JW, Chen JS, Shun CT, et al (2009). Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol, 129, 1016-25.   DOI
32 Torres MP, Ponnusamy MP, Lakshmanan I, et al (2009). Immunopathogenesis of ovarian cancer. Minerva Medica, 100, 385-400.
33 Wang J, Xiao L, Luo CH, et al (2014). Overexpression of TRPM7 is associated with poor prognosis in human ovarian carcinoma. Asian Pac J Cancer Prev, 15, 3955-8.   과학기술학회마을   DOI
34 Wang YH, Cao YW, Yang XC, et al (2014). Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance. Asian Pac J Cancer Prev, 15, 1321-6.   과학기술학회마을   DOI
35 Whitworth JM, Alvarez RD (2011). Evaluating the role of IL-12 based therapies in ovarian cancer: a review of the literature. Expert Opin. Biol. Ther, 11, 751-62.   DOI
36 Wintterle S, Schreiner B, Mitsdoerffer M, et al (2003). Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res, 63, 7462-7.
37 Wu K, Kryczek I, Chen LP, et al (2009). Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1 programmed death-1 interactions. Cancer Res, 69, 8067-75.   DOI
38 Wu P, Liang DH, Liu YF, et al (2009). [Effects of high-density lipoprotein 1 on the formation of foam cells from human monocyte-derived macrophages]. Zhonghua Xin Xue Guan Bing Za Zhi, 37 156-60.
39 Elhag OAO, Hu XJ, Zhang WY, et al (2012). Reconstructed adeno-associated virus with the extracellular domain of murine PD-1 induces antitumor immunity. Asian Pac J Cancer Prev, 13, 4031-6.   과학기술학회마을   DOI
40 Puddu P, Fantuzzi L, Borghi P, et al (1997). IL-12 induces IFN-gamma expression and secretion in mouse peritoneal macrophages. J Immunol, 159, 3490-7.