Increase of IFN-γ and TNF-α production in CD107a + NK-92 cells co-cultured with cervical cancer cell lines pre-treated with the HO-1 inhibitor

Cancer Cell International

Pablo Cesar Ortiz-Lazareno¹  Karina Sánchez-Reyes²  Jorge Ramiro Domínguez-Rodríguez³  José Manuel Lerma-Díaz⁴  Adriana Aguilar-Lemarroy¹  Luis Felipe Jave-Suárez¹  Georgina Hernández-Flores¹  Alejandro Bravo-Cuellar⁴  Paulina Gómez-Lomelí² 

[1] División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, Guadalajara, 44340, Jalisco, Mexico;Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), UdeG, Guadalajara, Jalisco, Mexico;Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingeniería, UdeG, Guadalajara, Jalisco, Mexico;Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara (UdeG), Tepatitlán de Morelos, Jalisco, Mexico

关键词: NKG2D;    NKp30;    TNF-α;    IFN-γ;    Cervical cancer cells;    NK cells;    Heme oxygenase 1;   

Others  :  1121652
DOI  :  10.1186/s12935-014-0100-1

 received in 2014-02-01, accepted in 2014-09-22,  发布年份 2014

【 摘 要 】

Background

Natural killer (NK) cells eliminate virus-infected and tumor cells through the release of perforins and granzymes; they also produce Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α), which induce apoptosis in target cells. Many tumors express Heme oxygenase 1 (HO-1), and this expression has been associated with avoiding immunosuppression and apoptosis. In this work, HO-1+ Cervical cancer cell (CCC) lines were pre-treated with HO-1 inhibitor and we assessed whether this inhibition enhanced the sensitivity of CCC to NK cell activity.

Methods

We assessed the expression of HO-1 in HeLa, SiHa, and C-33A CCC by Flow cytometry (FC). CCC were pre-treated with SnPP or ZnPP HO-1 inhibitors. After that, NK-92 cells were co-cultured with HeLa, SiHa, and C-33A CCC pre-treated or not with HO-1 inhibitors, and the expression of IFN-γ, TNF-α, CD107a, Granzyme B, NKp44, NKp46, NKp30, and NKG2D was evaluated by FC.

Results

CCC lines HeLa, SiHa, and C-33A expressed HO-1. Inhibition of HO-1 in these cells increased the expression of IFN-γ and TNF-α in CD107a + NK-92 cells. We observed a reduction in the expression of NKG2D, NKp46, and NKp30 in NK cells co-cultured with HeLa and SiHa cells, and when HeLa and SiHa cells were pre-treated with the HO-1 inhibitors, the expression of NKG2D and NKp30 in NK cells was restored. We observed a similar effect in NK cells co-cultured with C-33A cells in NKp30 expression.

Conclusion

Inhibition of HO-1 in CCC induces an increase in IFN-γ and TNF-α production in CD107a + NK-92 cells and restores NKG2D, NKp46 and NKp30 downmodulation in NK cells.

【 授权许可】

   
2014 Gómez-Lomeli et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61(2):69-90.
• [2]Jayshree R, Sreenivas A, Tessy M, Krishna S: Cell intrinsic & extrinsic factors in cervical carcinogenesis.pdf. Indian J Med Res 2009, 130:286-295.
• [3]Schiffman M, Castle P, Jeronimo J, Rodriguez A, Wacholder S: Human papillomavirus and cervical cancer. Lancet 2007, 370(9590):890-907.
• [4]Jabbour H, Sales K, Catalano R, Norman J: Inflammatory pathways in female reproductive health and disease. Reproduction (Cambridge, England) 2009, 138(6):903-919.
• [5]Levy E, Roberti M, Mordoh J: Natural killer cells in human cancer: from biological functions to clinical applications. J Biomed Biotechnol 2011, 2011:676198.
• [6]Baier C, Fino A, Sanchez C, Farnault L, Rihet P, Kahn-Perles B, Costello RT: Natural killer cells modulation in hematological malignancies. Front Immunol 2013, 4:459.
• [7]Seeger P, Bosisio D, Parolini S, Badolato R, Gismondi A, Santoni A, Sozzani S: Activin A as a mediator of NK-Dendritic cell functional interactions. J Immunol 2014, 192(3):1241-1248.
• [8]Gross E, Sunwoo JB, Bui JD: Cancer immunosurveillance and immunoediting by natural killer cells. Cancer J 2013, 19(6):483-489.
• [9]Sun JC, Lanier LL: NK cell development, homeostasis and function: parallels with CD8+ T cells. Nat Rev Immunol 2011, 11(10):645-657.
• [10]Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, Balsamo M, Conte R, Benelli R, Minghelli S, Solari N, Gualco M, Queirolo P, Moretta L, Mingari MC: Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res 2012, 72(6):1407-1415.
• [11]Bryceson YT, Chiang SC, Darmanin S, Fauriat C, Schlums H, Theorell J, Wood SM: Molecular mechanisms of natural killer cell activation. J Innate Immun 2011, 3(3):216-226.
• [12]Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T: Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999, 285(5428):727-729.
• [13]Cosman D, Mullberg J, Sutherland CL, Chin W, Armitage R, Fanslow W, Kubin M, Chalupny NJ: ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 2001, 14(2):123-133.
• [14]Pogge von Strandmann E, Simhadri VR, von Tresckow B, Sasse S, Reiners KS, Hansen HP, Rothe A, Boll B, Simhadri VL, Borchmann P, McKinnon PJ, Hallek M, Engert A: Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 2007, 27(6):965-974.
• [15]Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B, Haldeman B, Ostrander CD, Kaifu T, Chabannon C, Moretta A, West R, Xu W, Vivier E, Levin SD: The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med 2009, 206(7):1495-1503.
• [16]Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD: Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002, 3(11):991-998.
• [17]Teague RM, Kline J: Immune evasion in acute myeloid leukemia: current concepts and future directions. J Immunotherapy of Cancer 2013, 1(13):1-13.
• [18]Patel S, Chiplunkar S: Host immune responses to cervical cancer. Curr Opin Obstet Gynecol 2009, 21(1):54-59.
• [19]Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou J, Anegon I, Cuturi M: A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007, 110(10):3691-3694.
• [20]Piantadosi C, Withers C, Bartz R, MacGarvey N, Fu P, Sweeney T, Welty-Wolf K, Suliman H: Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. J Biol Chem 2011, 286(18):16374-16385.
• [21]Ryter S, Alam J, Choi A: Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006, 86(2):583-650.
• [22]Berberat P, Dambrauskas Z, Gulbinas A, Giese T, Giese N, Künzli B, Autschbach F, Meuer S, Büchler M, Friess H: Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment. Clin Cancer Res 2005, 11(10):3790-3798.
• [23]Castronuovo C, Sacca P, Meiss R, Caballero F, Batlle A, Vazquez E: Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association. BMC Cancer 2006, 6:286. BioMed Central Full Text
• [24]Wang LH, Li Y, Yang SN, Wang FY, Hou Y, Cui W, Chen K, Cao Q, Wang S, Zhang TY, Wang ZZ, Xiao W, Yang JY, Wu CF: Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-kappaB and MAPK/HO-1 signalling. Br J Cancer 2013, 110:341-352.
• [25]Rushworth SA, Bowles KM, Raninga P, MacEwan DJ: NF-kappaB-inhibited acute myeloid leukemia cells are rescued from apoptosis by heme oxygenase-1 induction. Cancer Res 2010, 70(7):2973-2983.
• [26]Goodman AI, Choudhury M, da Silva JL, Schwartzman ML, Abraham NG: Overexpression of the heme oxygenase gene in renal cell carcinoma. Proc Soc Exp Biol Med 1997, 214(1):54-61.
• [27]Simon T, Anegon I, Blancou P: Heme oxygenase and carbon monoxide as an immunotherapeutic approach in transplantation and cancer. Immunotherapy 2011, 3(4s):15-18.
• [28]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-674.
• [29]Camara NO, Soares MP: Heme oxygenase-1 (HO-1), a protective gene that prevents chronic graft dysfunction. Free Radic Biol Med 2005, 38(4):426-435.
• [30]Otterbein LE, Soares MP, Yamashita K, Bach FH: Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 2003, 24(8):449-455.
• [31]Yamashita K, Öllinger R, McDaid J, Sakahama H, Wang H, Tyagi S, Csizmadia E, Smith NR, Soares MP, Bach FH: Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs. FASEB J 2006, 20(6):776-778.
• [32]Tamion F, Richard V, Renet S, Thuillez C: Protective effects of heme-oxygenase expression against endotoxic shock: inhibition of tumor necrosis factor-alpha and augmentation of interleukin-10. J Trauma 2006, 61(5):1078-1084.
• [33]Lewkowicz N, Klink M, Mycko MP, Lewkowicz P: Neutrophil–CD4 + CD25+ T regulatory cell interactions: a possible new mechanism of infectious tolerance. Immunobiology 2013, 218(4):455-464.
• [34]Was H, Dulak J, Jozkowicz A: Heme oxygenase-1 in tumor biology and therapy. Curr Drug Targets 2010, 11(12):1551-1570.
• [35]Weis N, Weigert A, von Knethen A, Brune B: Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants. Mol Biol Cell 2009, 20(5):1280-1288.
• [36]James N, Arnold LM, Kraman M, Fearon D: Tumoral Immune Suppression by Macrophages Expressing Fibroblast Activation Protein-Alpha and Heme Oxygenase-1. Cancer Immunology Res 2014, 2(2):121-126.
• [37]Blancou P, Anegon I: Editorial: Heme oxygenase-1 and dendritic cells: what else? J Leukoc Biol 2010, 87(2):185-187.
• [38]Orange JS: Formation and function of the lytic NK-cell immunological synapse. Nat Rev Immunol 2008, 8(9):713-725.
• [39]Aktas E, Kucuksezer UC, Bilgic S, Erten G, Deniz G: Relationship between CD107a expression and cytotoxic activity. Cell Immunol 2009, 254(2):149-154.
• [40]Alter G, Malenfant JM, Altfeld M: CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 2004, 294(1):15-22.
• [41]Viel S, Charrier E, Marcais A, Rouzaire P, Bienvenu J, Karlin L, Salles G, Walzer T: Monitoring NK cell activity in patients with hematological malignancies. Oncoimmunology 2013, 2(9):e26011.
• [42]Kollipara PS, Kim JH, Won D, Lee SM, Sung HC, Chang HS, Lee KT, Lee KS, Park MH, Song MJ, Song HS, Hong JT: Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-kappaB. Arch Pharm Res 2014, 37(3):379-389.
• [43]Song DZ, Liang Y, Xiao Q, Yin J, Gong JL, Lai ZP, Zhang ZF, Gao LX, Fan XH: TRAIL is involved in the tumoricidal activity of mouse natural killer cells stimulated by Newcastle disease virus in vitro. Anat Rec 2013, 296(10):1552-1560.
• [44]Pae H-O, Oh G-S, Choi B-M, Chae S-C, Kim Y-M, Chung K-R, Chung H-T: Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol 2004, 172(8):4744-4751.
• [45]Lee TS, Chau LY: Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002, 8(3):240-246.
• [46]Sawle P, Foresti R, Mann BE, Johnson TR, Green CJ, Motterlini R: Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br J Pharmacol 2005, 145(6):800-810.
• [47]Wu J, Lanier LL: Natural killer cells and cancer. Adv Cancer Res 2003, 90:127-156.
• [48]Smyth MJ, Hayakawa Y, Takeda K, Yagita H: New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2002, 2(11):850-861.
• [49]Fluhr H, Krenzer S, Stein GM, Stork B, Deperschmidt M, Wallwiener D, Wesselborg S, Zygmunt M, Licht P: Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis. J Cell Sci 2007, 120(Pt 23):4126-4133.
• [50]Martin-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, Sallusto F: Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol 2004, 5(12):1260-1265.
• [51]Woodworth CD: HPV innate immunity. Front Biosci 2002, 7:d2058-d2071.
• [52]Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z: Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 2008, 180(11):7249-7258.
• [53]Verhoeven AJ, Jansen H: Secretion-coupled increase in the catalytic activity of rat hepatic lipase. Biochim Biophys Acta 1991, 1086(1):49-56.
• [54]Jimenez-Perez MI, Jave-Suarez LF, Ortiz-Lazareno PC, Bravo-Cuellar A, Gonzalez-Ramella O, Aguilar-Lemarroy A, Hernandez-Flores G, Pereira-Suarez AL, Daneri-Navarro A, del Toro-Arreola S: Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. BMC Immunol 2012, 13:7. BioMed Central Full Text
• [55]Garcia-Iglesias T, Del Toro-Arreola A, Albarran-Somoza B, Del Toro-Arreola S, Sanchez-Hernandez PE, Ramirez-Duenas MG, Balderas-Pena LM, Bravo-Cuellar A, Ortiz-Lazareno PC, Daneri-Navarro A: Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer 2009, 9:186. BioMed Central Full Text