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The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

Cellular & Molecular Immunology volume 12, pages 326–341 (2015)Cite this article

Abstract

Interferon gamma (IFN-γ) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-γ induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-γ on macrophage activation. IFN-γ reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT+LIF cells) and BeWo cells (BW/ST+LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-γ. vCT+LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST+LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-γ on monocyte/macrophage motility. BW/ST+LIF cells also generate IFN-γ-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-α), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-γ-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF–trophoblast–IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.

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References

  1. Mosser DM . The many faces of macrophage activation. J Leuk Biol 2003; 73: 209–212.

    Article  CAS  Google Scholar 

  2. Gordon S . Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23–35.

    Article  CAS  PubMed  Google Scholar 

  3. Cohen HB, Mosser DM . Extrinsic and intrinsic control of macrophage inflammatory responses. J Leuk Biol 2013; 94: 913–919.

    Article  CAS  Google Scholar 

  4. Mosser DM, Zhang X . Activation of murine macrophages. Curr Protoc Immunol 2008; Chapter 14: Unit 14 2.

    PubMed  Google Scholar 

  5. Yang Z, Kong B, Mosser DM, Zhang X . TLRs, macrophages, and NK cells: our understandings of their functions in uterus and ovary. Int Immunopharmacol 2011; 11: 1442–1450.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang X, Mosser DM . Macrophage activation by endogenous danger signals. J Pathol 2008; 214: 161–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nagamatsu T, Schust DJ . The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010; 63: 460–471.

    Article  CAS  PubMed  Google Scholar 

  8. Renaud SJ, Graham CH . The role of macrophages in utero–placental interactions during normal and pathological pregnancy. Immunol Invest 2008; 37: 535–564.

    Article  CAS  PubMed  Google Scholar 

  9. Gustafsson C, Mjosberg J, Matussek A, Geffers R, Matthiesen L, Berg G et al. Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLoS ONE 2008; 3: e2078.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Svensson J, Jenmalm MC, Matussek A, Geffers R, Berg G, Ernerudh J . Macrophages at the fetal–maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J Immunol 2011; 187: 3671–3682.

    Article  CAS  PubMed  Google Scholar 

  11. Heikkinen J, Mottonen M, Komi J, Alanen A, Lassila O . Phenotypic characterization of human decidual macrophages. Clin Exp Immunol 2003; 131: 498–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wu ZM, Yang H, Li M, Yeh CC, Schatz F, Lockwood CJ et al. Pro-inflammatory cytokine-stimulated first trimester decidual cells enhance macrophage-induced apoptosis of extravillous trophoblasts. Placenta 2012; 33: 188–194.

    Article  PubMed  Google Scholar 

  13. Granot I, Gnainsky Y, Dekel N . Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction 2012; 144: 661–668.

    Article  CAS  PubMed  Google Scholar 

  14. Mor G, Cardenas I, Abrahams V, Guller S . Inflammation and pregnancy: the role of the immune system at the implantation site. Ann NY Acad Sci 2011; 1221: 80–87.

    Article  CAS  PubMed  Google Scholar 

  15. Boehm U, Klamp T, Groot M, Howard JC . Cellular responses to interferon-gamma. Annu Rev Immunol 1997; 15: 749–795.

    Article  CAS  PubMed  Google Scholar 

  16. Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA . Interferon gamma in successful pregnancies. Biol Reprod 2009; 80: 848–859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Clark DA, Chaouat G, Arck PC, Mittruecker HW, Levy GA . Cytokine-dependent abortion in CBA×DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase]. J Immunol 1998; 160: 545–549.

    CAS  PubMed  Google Scholar 

  18. Gendron RL, Nestel FP, Lapp WS, Baines MG . Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha. J Reprod Fertil 1990; 90: 395–402.

    Article  CAS  PubMed  Google Scholar 

  19. Murphy SP, Fast LD, Hanna NN, Sharma S . Uterine NK cells mediate inflammation-induced fetal demise in IL-10-null mice. J Immunol 2005; 175: 4084–4090.

    Article  CAS  PubMed  Google Scholar 

  20. Murphy SP, Hanna NN, Fast LD, Shaw SK, Berg G, Padbury JF et al. Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery. Am J Obstetr Gynecol 2009; 200: 308.e1–308.e9.

    Article  Google Scholar 

  21. Haddad EK, Duclos AJ, Lapp WS, Baines MG . Early embryo loss is associated with the prior expression of macrophage activation markers in the decidua. J Immunol 1997; 158: 4886–4892.

    CAS  PubMed  Google Scholar 

  22. Fest S, Aldo PB, Abrahams VM, Visintin I, Alvero A, Chen R et al. Trophoblast–macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod immunol 2007; 57: 55–66.

    Article  PubMed  Google Scholar 

  23. Dimitriadis E, White CA, Jones RL, Salamonsen LA . Cytokines, chemokines and growth factors in endometrium related to implantation. Hum Reprod Update 2005; 11: 613–630.

    Article  CAS  PubMed  Google Scholar 

  24. Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N et al. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod 2007; 76: 102–117.

    Article  CAS  PubMed  Google Scholar 

  25. Kimber SJ . Leukaemia inhibitory factor in implantation and uterine biology. Reproduction 2005; 130: 131–145.

    Article  CAS  PubMed  Google Scholar 

  26. Weber MA, Schnyder-Candrian S, Schnyder B, Quesniaux V, Poli V, Stewart CL et al. Endogenous leukemia inhibitory factor attenuates endotoxin response. Lab Invest 2005; 85: 276–284.

    Article  CAS  PubMed  Google Scholar 

  27. Aisemberg J, Vercelli CA, Bariani MV, Billi SC, Wolfson ML, Franchi AM . Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone. PLoS ONE 2013; 8: e56161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Szony BJ, Bata-Csorgo Z, Bartfai G, Kemeny L, Dobozy A, Kovacs L . Interleukin-10 receptors are expressed by basement membrane anchored, alpha6) integrin+ cytotrophoblast cells in early human placenta. Mol Hum Reprod 1999; 5: 1059–1065.

    Article  CAS  PubMed  Google Scholar 

  29. Thaxton JE, Sharma S . Interleukin-10: a multi-faceted agent of pregnancy. Am J Reprod Immunol 2010; 63: 482–491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D'Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G . Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 1993; 178: 1041–1048.

    Article  CAS  PubMed  Google Scholar 

  31. Wang P, Wu P, Siegel MI, Egan RW, Billah MM . IL-10 inhibits transcription of cytokine genes in human peripheral blood mononuclear cells. J Immunol 1994; 153: 811–816.

    CAS  PubMed  Google Scholar 

  32. Dealtry GB, O'Farrell MK, Fernandez N . The Th2 cytokine environment of the placenta. Int Arch Allergy Immunol 2000; 123: 107–119.

    Article  CAS  PubMed  Google Scholar 

  33. O'Farrell AM, Liu Y, Moore KW, Mui AL . IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways. EMBO J 1998; 17: 1006–1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ito S, Ansari P, Sakatsume M, Dickensheets H, Vazquez N, Donnelly RP et al. Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 1999; 93: 1456–1463.

    CAS  PubMed  Google Scholar 

  35. Sharkey AM, King A, Clark DE, Burrows TD, Jokhi PP, Charnock-Jones DS et al. Localization of leukemia inhibitory factor and its receptor in human placenta throughout pregnancy. Biol Reprod 1999; 60: 355–364.

    Article  CAS  PubMed  Google Scholar 

  36. Dufresne M, Dumas G, Asselin E, Carrier C, Pouliot M, Reyes-Moreno C . Pro-inflammatory type-1 and anti-inflammatory type-2 macrophages differentially modulate cell survival and invasion of human bladder carcinoma T24 cells. Mol Immunol 2011; 48: 1556–1567.

    Article  CAS  PubMed  Google Scholar 

  37. Dumas G, Dufresne M, Asselin E, Girouard J, Carrier C, Reyes-Moreno C . CD40 pathway activation reveals dual function for macrophages in human endometrial cancer cell survival and invasion. Cancer Immunol Immunother 2012; 62: 273–283.

    Article  PubMed  Google Scholar 

  38. Leduc K, Bourassa V, Asselin E, Leclerc P, Lafond J, Reyes-Moreno C . Leukemia inhibitory factor regulates differentiation of trophoblastlike BeWo cells through the activation of JAK/STAT and MAPK3/1 MAP kinase-signaling pathways. Biol Reprod 2012; 86: 54.

    Article  PubMed  Google Scholar 

  39. Lanoix D, Beghdadi H, Lafond J, Vaillancourt C . Human placental trophoblasts synthesize melatonin and express its receptors. J Pineal Res 2008; 45: 50–60.

    Article  CAS  PubMed  Google Scholar 

  40. Lanoix D, Vaillancourt C . Cell culture media formulation and supplementation affect villous trophoblast HCG release. Placenta 2010; 31: 558–559.

    Article  CAS  PubMed  Google Scholar 

  41. Le Bellego F, Vaillancourt C, Lafond J . Isolation and culture of term human cytotrophoblast cells and in vitro methods for studying human cytotrophoblast cells' calcium uptake. Methods Mol Biol 2009; 550: 73–87.

    Article  CAS  PubMed  Google Scholar 

  42. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B . The choriocarcinoma cell line BeWo: syncytial fusion and expression of syncytium-specific proteins. Reproduction 2010; 140: 759–766.

    Article  CAS  PubMed  Google Scholar 

  43. Liu F, Soares MJ, Audus KL . Permeability properties of monolayers of the human trophoblast cell line BeWo. Am J Physiol 1997; 273: C1596–C1604.

    Article  CAS  PubMed  Google Scholar 

  44. Wice B, Menton D, Geuze H, Schwartz AL . Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 1990; 186: 306–316.

    Article  CAS  PubMed  Google Scholar 

  45. Bennett WA, Lagoo-Deenadayalan S, Brackin MN, Hale E, Cowan BD . Cytokine expression by models of human trophoblast as assessed by a semiquantitative reverse transcription-polymerase chain reaction technique. Am J Reprod Immunol 1996; 36: 285–294.

    Article  CAS  PubMed  Google Scholar 

  46. Bennett WA, Lagoo-Deenadayalan S, Whitworth NS, Brackin MN, Hale E, Cowan BD . Expression and production of interleukin-10 by human trophoblast: relationship to pregnancy immunotolerance. Early Pregnancy 1997; 3: 190–198.

    CAS  PubMed  Google Scholar 

  47. Zhao M, Zhang R, Xu X, Liu Y, Zhang H, Zhai X et al. IL-10 reduces levels of apoptosis in Toxoplasma gondii-infected trophoblasts. PloS ONE 2013; 8: e56455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ansa-Addo EA, Lange S, Stratton D, Antwi-Baffour S, Cestari I, Ramirez MI et al. Human plasma membrane-derived vesicles halt proliferation and induce differentiation of THP-1 acute monocytic leukemia cells. J Immunol 2010; 185: 5236–5246.

    Article  CAS  PubMed  Google Scholar 

  49. Auwerx J . The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia 1991; 47: 22–31.

    Article  CAS  PubMed  Google Scholar 

  50. Qin Z . The use of THP-1 cells as a model for mimicking the function and regulation of monocytes and macrophages in the vasculature. Atherosclerosis 2012; 221: 2–11.

    Article  CAS  PubMed  Google Scholar 

  51. Daigneault M, Preston JA, Marriott HM, Whyte MK, Dockrell DH . The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS ONE 2010; 5: 0008668.

    Article  Google Scholar 

  52. Menon MB, Ronkina N, Schwermann J, Kotlyarov A, Gaestel M . Fluorescence-based quantitative scratch wound healing assay demonstrating the role of MAPKAPK-2/3 in fibroblast migration. Cell Motil Cytoskeleton 2009; 66: 1041–1047.

    Article  CAS  PubMed  Google Scholar 

  53. Penton-Rol G, Polentarutti N, Luini W, Borsatti A, Mancinelli R, Sica A et al. Selective inhibition of expression of the chemokine receptor CCR2 in human monocytes by IFN-γ. J Immunol 1998; 160: 3869–3873.

    CAS  PubMed  Google Scholar 

  54. Ashkar AA, Di Santo JP, Croy BA . Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 2000; 192: 259–270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Klimp AH, de Vries EG, Scherphof GL, Daemen T . A potential role of macrophage activation in the treatment of cancer. Crit Rev Oncol Hematol 2002; 44: 143–161.

    Article  CAS  PubMed  Google Scholar 

  56. Bode JG, Ehlting C, Haussinger D . The macrophage response towards LPS and its control through the p38(MAPK)–STAT3 axis. Cell Signal 2012; 24: 1185–1194.

    Article  CAS  PubMed  Google Scholar 

  57. Tamai R, Sugawara S, Takeuchi O, Akira S, Takada H . Synergistic effects of lipopolysaccharide and interferon-gamma in inducing interleukin-8 production in human monocytic THP-1 cells is accompanied by up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression. J Endotoxin Res 2003; 9: 145–153.

    Article  CAS  PubMed  Google Scholar 

  58. Friebe A, Douglas AJ, Solano E, Blois SM, Hagen E, Klapp BF et al. Neutralization of LPS or blockage of TLR4 signaling prevents stress-triggered fetal loss in murine pregnancy. J Mol Med (Berl) 2011; 89: 689–699.

    Article  CAS  Google Scholar 

  59. Reyes-Moreno C, Girouard J, Lapointe R, Darveau A, Mourad W . CD40/CD40 homodimers are required for CD40-induced phosphatidylinositol 3-kinase-dependent expression of B7.2 by human B lymphocytes. J Biol Chem 2004; 279: 7799–7806.

    Article  CAS  PubMed  Google Scholar 

  60. Reyes-Moreno C, Sharif-Askari E, Girouard J, Leveille C, Jundi M, Akoum A et al. Requirement of oxidation-dependent CD40 homodimers for CD154/CD40 bidirectional signaling. J Biol Chem 2007; 282: 19473–19480.

    Article  CAS  PubMed  Google Scholar 

  61. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G . Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T–T help via APC activation. J Exp Med 1996; 184: 747–752.

    Article  CAS  PubMed  Google Scholar 

  62. Lee SJ, Qin H, Benveniste EN . Simvastatin inhibits IFN-gamma-induced CD40 gene expression by suppressing STAT-1alpha. J Leukoc Biol 2007; 82: 436–447.

    Article  CAS  PubMed  Google Scholar 

  63. Sayama S, Nagamatsu T, Schust DJ, Itaoka N, Ichikawa M, Kawana K et al. Human decidual macrophages suppress IFN-gamma production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy. J Reprod Immunol 2013; 100: 109–117.

    Article  CAS  PubMed  Google Scholar 

  64. Co EC, Gormley M, Kapidzic M, Rosen DB, Scott MA, Stolp HA et al. Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy. Biol Reprod 2013; 88: 155.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD . How cells respond to interferons. Annu Rev Biochem 1998; 67: 227–264.

    Article  CAS  PubMed  Google Scholar 

  66. Hu Y, Hu X, Boumsell L, Ivashkiv LB . IFN-γ and STAT1 arrest monocyte migration and modulate RAC/CDC42 pathways. J Immunol 2008; 180: 8057–8065.

    Article  CAS  PubMed  Google Scholar 

  67. Chen CW, Chang YH, Tsi CJ, Lin WW . Inhibition of IFN-gamma-mediated inducible nitric oxide synthase induction by the peroxisome proliferator-activated receptor gamma agonist, 15-deoxy-delta 12,14-prostaglandin J2, involves inhibition of the upstream Janus kinase/STAT1 signaling pathway. J Immunol 2003; 171: 979–988.

    Article  CAS  PubMed  Google Scholar 

  68. Takaki H, Minoda Y, Koga K, Takaesu G, Yoshimura A, Kobayashi T . TGF-beta1 suppresses IFN-gamma-induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation. Genes Cells 2006; 11: 871–882.

    Article  CAS  PubMed  Google Scholar 

  69. Renaud SJ, Sullivan R, Graham CH . Tumour necrosis factor alpha stimulates the production of monocyte chemoattractants by extravillous trophoblast cells via differential activation of MAPK pathways. Placenta 2009; 30: 313–319.

    Article  CAS  PubMed  Google Scholar 

  70. Hu X, Park-Min KH, Ho HH, Ivashkiv LB . IFN-gamma-primed macrophages exhibit increased CCR2-dependent migration and altered IFN-gamma responses mediated by Stat1. J Immunol 2005; 175: 3637–3647.

    Article  CAS  PubMed  Google Scholar 

  71. Oliveira LJ, McClellan S, Hansen PJ . Differentiation of the endometrial macrophage during pregnancy in the cow. PLoS ONE 2010; 5: e13213.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kim JS, Kim JG, Moon MY, Jeon CY, Won HY, Kim HJ et al. Transforming growth factor-beta1 regulates macrophage migration via RhoA. Blood 2006; 108: 1821–1829.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT) and the Réseau Québécois en Reproduction (RQR) to CR-M AD, RD and JH-M were supported by the RQR-CREATE scholarships program. JG holds a postdoctoral fellowship from the Fonds de la Recherche en Santé du Québec (FRSQ). The authors wish to acknowledge Nahla Mrad and Rodrigo Flores Soto for technical assistance in cell signaling and cell motility studies as well as Dr Monique Cadrin and Dr Céline Van Themsche for critical reading of this manuscript.

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  1. département de biologie médicale, Groupe de Recherche en Oncologie et Endocrinologie Moléculaires, Université du Québec à Trois-Rivières, Trois-Rivières, G9A 5H7, PQ, Canada

    Angham Dallagi, Julie Girouard, Jovane Hamelin-Morrissette, Rachel Dadzie & Carlos Reyes-Moreno

  2. Centre de recherche BioMed UQAM-UQTR-INRS, Montréal, H3C 3P8, PQ, Canada

    Angham Dallagi, Julie Girouard, Jovane Hamelin-Morrissette, Rachel Dadzie, Laetitia Laurent, Cathy Vaillancourt, Julie Lafond & Carlos Reyes-Moreno

  3. INRS-Institut Armand-Frappier, Université du Québec, Laval, H7V 1B7, PQ, Canada

    Laetitia Laurent & Cathy Vaillancourt

  4. département des sciences biologiques, Université du Québec à Montréal, Montréal, H3C 3P8, QC, Canada

    Julie Lafond

  5. Centre Hospitalier Régional de Trois-Rivières, Trois-Rivières, G9A 1Y1, PQ, Canada

    Christian Carrier

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  1. Angham Dallagi
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Dallagi, A., Girouard, J., Hamelin-Morrissette, J. et al. The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation. Cell Mol Immunol 12, 326–341 (2015). https://doi.org/10.1038/cmi.2014.50

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