Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages

BMT

Biomaterials Translational

TBA2096-112X

Biomaterials Translational

10.12336/biomatertransl.2021.02.004

Research Article

Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophageshttps://artdesignp.com/journal/BMT/2/2/10.12336/biomatertransl.2021.02.004Rachel FrancisWendy,LiuZhao,E OwensSian,WangXiao,XueHuaming,LordAlex,KanamarlapudiVenkateswarlu,XiaZhidao

2021

2021-06-28

Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles (CoNPs) produced from wear cause inflammation, bone lyses and cytotoxicity at high concentrations. Cobalt ions mimic hypoxia in the presence of normal oxygen levels, and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α (HIF1α). This study aimed to assess in vitro the functional role of HIF1α in CoNP induced cellular cytotoxicity. HIF1α, lysosomal pH, tumour necrosis factor α and interleukin 1β expression were analysed in THP-1 macrophages treated with CoNP (0, 10 and 100 μg/mL). HIF1α knock out assays were performed using small interfering RNA to assess the role of HIF1α in CoNP-induced cytotoxicity. Increasing CoNP concentration increased lysosomal activity and acidity in THP-1 macrophages. Higher doses of CoNP significantly reduced cell viability, stimulated caspase 3 activity and apoptosis. Reducing HIF1α activity increased the pro-inflammatory activity of tumour necrosis factor α and interleukin 1β, but had no significant impact on cellular cytotoxicity. This suggests that whilst CoNP promotes cytotoxicity and cellular inflammation, the apoptotic mechanism is not dependent on HIF1α.cobalt nanoparticle ; cytotoxicity ; hypoxia inducible factor ; macrophages ; TNFα

1. Learmonth, I. D.; Young, C.; Rorabeck, C. The operation of the century: total hip replacement. *Lancet*, 2007, 370, 1508-1519. 2. O’Boyle, C. A.; McGee, H.; Hickey, A.; O’Malley, K.; Joyce, C. R. Individual quality of life in patients undergoing hip replacement. *Lancet*, 1992, 339, 1088-1091. 3. Samelko, L.; Caicedo, M. S.; Lim, S. J.; Della-Valle, C.; Jacobs, J.; Hallab, N. J. Cobalt-alloy implant debris induce HIF-1α hypoxia associated responses: a mechanism for metal-specific orthopedic implant failure. *PLoS One*, 2013, 8, e67127. 4. Schoon, J.; Hesse, B.; Rakow, A.; Ort, M. J.; Lagrange, A.; Jacobi, D.; Winter, A.; Huesker, K.; Reinke, S.; Cotte, M.; Tucoulou, R.; Marx, U.; Perka, C.; Duda, G. N.; Geissler, S. Metal-specific biomaterial accumulation in human peri-implant bone and bone marrow. *Adv Sci (Weinh)*, 2020, 7, 2000412. 5. Xia, Z.; Kwon, Y. M.; Mehmood, S.; Downing, C.; Jurkschat, K.; Murray, D. W. Characterization of metal-wear nanoparticles in pseudotumor following metal-on-metal hip resurfacing. *Nanomedicine*, 2011, 7, 674-681. 6. Junnila, M.; Seppänen, M.; Mokka, J.; Virolainen, P.; Pölönen, T.; Vahlberg, T.; Mattila, K.; Tuominen, E. K.; Rantakokko, J.; Äärimaa, V.; Itälä, A.; Mäkelä, K. T. Adverse reaction to metal debris after Birmingham hip resurfacing arthroplasty. *Acta Orthop*, 2015, 86, 345-350. 7. Lainiala, O.; Eskelinen, A.; Elo, P.; Puolakka, T.; Korhonen, J.; Moilanen, T. Adverse reaction to metal debris is more common in patients following MoM total hip replacement with a 36 mm femoral head than previously thought: results from a modern MoM follow-up program. *Bone Joint J*, 2014, 96-b, 1610-1617. 8. Langton, D. J.; Joyce, T. J.; Jameson, S. S.; Lord, J.; Van Orsouw, M.; Holland, J. P.; Nargol, A. V.; De Smet, K. A. Adverse reaction to metal debris following hip resurfacing: the influence of component type, orientation and volumetric wear. *J Bone Joint Surg Br*, 2011, 93, 164-171. 9. Xia, Z.; Ricciardi, B. F.; Liu, Z.; von Ruhland, C.; Ward, M.; Lord, A.; Hughes, L.; Goldring, S. R.; Purdue, E.; Murray, D.; Perino, G. Nano-analyses of wear particles from metal-on-metal and non-metal-on-metal dual modular neck hip arthroplasty. *Nanomedicine*, 2017, 13, 1205-1217. 10. Kwon, Y. M.; Xia, Z.; Glyn-Jones, S.; Beard, D.; Gill, H. S.; Murray, D. W. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro. *Biomed Mater*, 2009, 4, 025018. 11. Simonsen, L. O.; Harbak, H.; Bennekou, P. Cobalt metabolism and toxicology - a brief update. *Sci Total Environ*, 2012, 432, 210-215. 12. Lauwerys, R.; Lison, D. Health risks associated with cobalt exposure - an overview. *Sci Total Environ*, 1994, 150, 1-6. 13. Lison, D.; Lauwerys, R. Cobalt bioavailability from hard metal particles. Further evidence that cobalt alone is not responsible for the toxicity of hard metal particles. *Arch Toxicol*, 1994, 68, 528-531. 14. Wang, S.; Liu, F.; Zeng, Z.; Yang, H.; Jiang, H. The protective effect of bafilomycin A1 against cobalt nanoparticle-induced cytotoxicity and aseptic inflammation in macrophages in vitro. *Biol Trace Elem Res*, 2016, 169, 94-105. 15. Catelas, I.; Petit, A.; Vali, H.; Fragiskatos, C.; Meilleur, R.; Zukor, D. J.; Antoniou, J.; Huk, O. L. Quantitative analysis of macrophage apoptosis vs. necrosis induced by cobalt and chromium ions in vitro. *Biomaterials*, 2005, 26, 2441-2453. 16. Salib, C. G.; Lewallen, E. A.; Paradise, C. R.; Tibbo, M. E.; Robin, J. X.; Trousdale, W. H.; Morrey, L. M.; Xiao, J.; Turner, T. W.; Limberg, A. K.; Jay, A. G.; Thaler, R.; Dudakovic, A.; Sanchez-Sotelo, J.; Morrey, M. E.; Berry, D. J.; Lewallen, D. G.; van Wijnen, A. J.; Abdel, M. P. Molecular pathology of adverse local tissue reaction caused by metal-on-metal implants defined by RNA-seq. *Genomics*, 2019, 111, 1404-1411. 17. Vengellur, A.; LaPres, J. J. The role of hypoxia inducible factor 1-alpha in cobalt chloride induced cell death in mouse embryonic fibroblasts. *Toxicol Sci*, 2004, 82, 638-646. 18. Ke, Q.; Costa, M. Hypoxia-inducible factor-1 (HIF-1). *Mol Pharmacol*, 2006, 70, 1469-1480. 19. Dai, Z. J.; Gao, J.; Ma, X. B.; Yan, K.; Liu, X. X.; Kang, H. F.; Ji, Z. Z.; Guan, H. T.; Wang, X. J. Up-regulation of hypoxia inducible factor-1α by cobalt chloride correlates with proliferation and apoptosis in PC-2 cells. *J Exp Clin Cancer Res*, 2012, 31, 28. 20. Nyga, A.; Hart, A.; Tetley, T. D. Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages. *Nanotoxicology*, 2015, 9, 905-917. 21. DePedro, H. M.; Urayama, P. Using LysoSensor Yellow/Blue DND-160 to sense acidic pH under high hydrostatic pressures. *Anal Biochem*, 2009, 384, 359-361. 22. Hart, A. J.; Quinn, P. D.; Lali, F.; Sampson, B.; Skinner, J. A.; Powell, J. J.; Nolan, J.; Tucker, K.; Donell, S.; Flanagan, A.; Mosselmans, J. F. Cobalt from metal-on-metal hip replacements may be the clinically relevant active agent responsible for periprosthetic tissue reactions. *Acta Biomater*, 2012, 8, 3865-3873. 23. Williams, A.; Flynn, K. J.; Xia, Z.; Dunstan, P. R. Multivariate spectral analysis of pH SERS probes for improved sensing capabilities. *J Raman Spectrosc*, 2016, 47, 819-827. 24. Xia, Z.; Triffitt, J. T. A review on macrophage responses to biomaterials. *Biomed Mater*, 2006, 1, R1-9. 25. Liu, M.; Bell, S.; Segarra, M.; Steven Tay, N. H.; Will, G.; Saman, W.; Bruno, F. A eutectic salt high temperature phase change material: Thermal stability and corrosion of SS316 with respect to thermal cycling. *Sol Energy Mater Sol Cells*, 2017, 170, 1-7. 26. Jeong, J.; Han, Y.; Poland, C. A.; Cho, W. S. Response-metrics for acute lung inflammation pattern by cobalt-based nanoparticles. *Part Fibre Toxicol*, 2015, 12, 13. 27. Czarnek, K.; Terpiłowska, S.; Siwicki, A. K. Selected aspects of the action of cobalt ions in the human body. *Cent Eur J Immunol*, 2015, 40, 236-242. 28. Paukkeri, E. L.; Korhonen, R.; Hämäläinen, M.; Pesu, M.; Eskelinen, A.; Moilanen, T.; Moilanen, E. The inflammatory phenotype in failed metal-on-metal hip arthroplasty correlates with blood metal concentrations. *PLoS One*, 2016, 11, e0155121. 29. Majmundar, A. J.; Wong, W. J.; Simon, M. C. Hypoxia-inducible factors and the response to hypoxic stress. *Mol Cell*, 2010, 40, 294-309. 30. Matsuura, H.; Ichiki, T.; Ikeda, J.; Takeda, K.; Miyazaki, R.; Hashimoto, T.; Narabayashi, E.; Kitamoto, S.; Tokunou, T.; Sunagawa, K. Inhibition of prolyl hydroxylase domain-containing protein downregulates vascular angiotensin II type 1 receptor. *Hypertension*, 2011, 58, 386-393. 31. Salnikow, K.; Donald, S. P.; Bruick, R. K.; Zhitkovich, A.; Phang, J. M.; Kasprzak, K. S. Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. *J Biol Chem*, 2004, 279, 40337-40344. 32. Saini, Y.; Greenwood, K. K.; Merrill, C.; Kim, K. Y.; Patial, S.; Parameswaran, N.; Harkema, J. R.; LaPres, J. J. Acute cobalt-induced lung injury and the role of hypoxia-inducible factor 1alpha in modulating inflammation. *Toxicol Sci*, 2010, 116, 673-681. 33. Manke, A.; Wang, L.; Rojanasakul, Y. Mechanisms of nanoparticle-induced oxidative stress and toxicity. *Biomed Res Int*, 2013, 2013, 942916. 34. Risom, L.; Møller, P.; Loft, S. Oxidative stress-induced DNA damage by particulate air pollution. *Mutat Res*, 2005, 592, 119-137. 35. Papageorgiou, I.; Brown, C.; Schins, R.; Singh, S.; Newson, R.; Davis, S.; Fisher, J.; Ingham, E.; Case, C. P. The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. *Biomaterials*, 2007, 28, 2946-2958. 36. Catelas, I.; Petit, A.; Zukor, D. J.; Antoniou, J.; Huk, O. L. TNF-alpha secretion and macrophage mortality induced by cobalt and chromium ions in vitro - qualitative analysis of apoptosis. *Biomaterials*, 2003, 24, 383-391. 37. Xu, J. W.; Konttinen, Y. T.; Lassus, J.; Natah, S.; Ceponis, A.; Solovieva, S.; Aspenberg, P.; Santavirta, S. Tumor necrosis factor-alpha (TNF-alpha) in loosening of total hip replacement (THR). *Clin Exp Rheumatol*, 1996, 14, 643-648. 38. Cummins, E. P.; Berra, E.; Comerford, K. M.; Ginouves, A.; Fitzgerald, K. T.; Seeballuck, F.; Godson, C.; Nielsen, J. E.; Moynagh, P.; Pouyssegur, J.; Taylor, C. T. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. *Proc Natl Acad Sci U S A*, 2006, 103, 18154-18159. 39. Rius, J.; Guma, M.; Schachtrup, C.; Akassoglou, K.; Zinkernagel, A. S.; Nizet, V.; Johnson, R. S.; Haddad, G. G.; Karin, M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. *Nature*, 2008, 453, 807-811. 40. Cramer, T.; Yamanishi, Y.; Clausen, B. E.; Förster, I.; Pawlinski, R.; Mackman, N.; Haase, V. H.; Jaenisch, R.; Corr, M.; Nizet, V.; Firestein, G. S.; Gerber, H. P.; Ferrara, N.; Johnson, R. S. HIF-1alpha is essential for myeloid cell-mediated inflammation. *Cell*, 2003, 112, 645-657. 41. Bandarra, D.; Biddlestone, J.; Mudie, S.; Müller, H. A.; Rocha, S. HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. *Dis Model Mech*, 2015, 8, 169-181. 42. Catelas, I.; Petit, A.; Zukor, D. J.; Huk, O. L. Cytotoxic and apoptotic effects of cobalt and chromium ions on J774 macrophages - Implication of caspase-3 in the apoptotic pathway. *J Mater Sci Mater Med*, 2001, 12, 949-953. 43. Shi, Y.; Chang, M.; Wang, F.; Ouyang, X.; Jia, Y.; Du, H. Role and mechanism of hypoxia-inducible factor-1 in cell growth and apoptosis of breast cancer cell line MDA-MB-231. *Oncol Lett*, 2010, 1, 657-662. 44. Greijer, A. E.; van der Wall, E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. *J Clin Pathol*, 2004, 57, 1009-1014. 45. Palazon, A.; Goldrath, A. W.; Nizet, V.; Johnson, R. S. HIF transcription factors, inflammation, and immunity. *Immunity*, 2014, 41, 518-528.