Research Article
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Year 2021, Volume: 80 Issue: 1, 9 - 14, 15.06.2021

Abstract

Project Number

5737

References

  • 1. Knöfler M, Haider S, Saleh L, Pollheimer J, Gamage TKJB, James J. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci 2019;76:3479–96.
  • 2. Schoots MH, Gordijn SJ, Scherjon SA, van Goor H, Hillebrands J-L. Oxidative stress in placental pathology. Placenta 2018;69:153–61.
  • 3. Otun HA, Lash GE, Innes BA, Bulmer JN, Naruse K, Hannon T, et al. Effect of tumour necrosis factor-α in combination with interferon-γ on first trimester extravillous trophoblast invasion. J Reprod Immunol 2011;88:1–11.
  • 4. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci 2018;19:1496.
  • 5. Schütze S, Wiegmann K, Machleidt T, Krönke M. TNF-induced activation of NF-κB. Immunobiology 1995;193:193–203.
  • 6. Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol 2014;26:253–66.
  • 7. Wang L, Du F, Wang X. TNF-α induces two distinct caspase-8 activation pathways. Cell 2008;133(4):693-703.
  • 8. McCarty MF, O’Keefe JH, DiNicolantonio JJ. Pentoxifylline for vascular health: a brief review of the literature. Open Hear 2016;3:e000365.
  • 9. Samlaska CP, Winfield EA. Pentoxifylline. J Am Acad Dermatol 1994;30:603–21.
  • 10. Chen HL, Yang Y, Hu XL, Yelavarthi KK, Fishback JL, Hunt JS. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am J Pathol 1991;139(2):327-335..
  • 11. Guzel E, Basar M, Ocak N, Arici A, Kayisli UA. Bidirectional interaction between unfolded-protein-response key protein HSPA5 and estrogen signaling in human endometrium. Biol Reprod 2011;85:121–7.
  • 12. Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O, et al. Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies? Placenta 2011;32:S4–16.
  • 13. Roberts JM, Gammill HS. Preeclampsia. Hypertension 2005;46:1243–9.
  • 14. Uzun M, Gencer M, Turkon H, Oztopuz RO, Demir U, Ovali MA. Effects of melatonin on blood pressure, oxidative stress and placental expressions of TNFα, IL-6, VEGF and sFlt-1 in RUPP rat model of preeclampsia. Arch Med Res 2017;48:592–8.
  • 15. Raghupathy R. Cytokines as key players in the pathophysiology of preeclampsia. Med Princ Pract 2013;22:8–19.
  • 16. Weel IC, Baergen RN, Romão-Veiga M, Borges VT, Ribeiro VR, Witkin SS, et al. Association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia. PLoS One 2016;11:e0157584.
  • 17. Qin ZH, Wang Y, Kikly KK, Sapp E, Kegel KB, Aronin N, et al. Pro-caspase-8 is predominantly localized in mitochondria and released into cytoplasm upon apoptotic stimulation. J Biol Chem 2001.
  • 18. Boldin MP, Goncharov TM, Goltsev Y V., Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996;85:803–815.
  • 19. Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 1996;85:817–827.
  • 20. Collins JA, Schandl CA, Young KK, Vesely J, Willingham MC. Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem 1997;45(7):923-934.
  • 21. Albensi BC. What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion? Front Cell Dev Biol 2019;7.
  • 22. Durand JK, Baldwin AS. Targeting IKK and NF-κB for therapy. Adv Protein Chem Struct Biol 2017, p. 77–115.
  • 23. Kniss DA, Rovin B, Fertel RH, Zimmerman PD. Blockade NF-κB activation prohibits TNF-α-induced cyclooxygenase-2 gene expression in ED27 trophoblast-like cells. Placenta 2001.
  • 24. Armistead B, Kadam L, Drewlo S, Kohan-Ghadr HR. The role of NFκB in healthy and preeclamptic placenta: Trophoblasts in the spotlight. Int J Mol Sci 2020.
  • 25. Ciuffetti G, Mercuri M, Ott C, Lombardini R, Paltriccia R, Lupattelli G, et al. Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease. Eur J Clin Pharmacol 1991;41:511–5.
  • 26. Hendawy N. Pentoxifylline attenuates cytokine stress and Fas system in syngeneic liver proteins induced experimental autoimmune hepatitis. Biomed Pharmacother 2017;92:316–23.
  • 27. Muchhala SK, Benzeroual KE. Pentoxifylline suppressed LPS-induced inflammatory and apoptotic signaling in neuronal cells. Adv Biosci Biotechnol 2012;03:731–9.
  • 28. Chen YM, Tu CJ, Hung KY, Wu KD, Tsai TJ, Hsieh BS. Inhibition by pentoxifylline of TNF-α-stimulated fractalkine production in vascular smooth muscle cells: Evidence for mediation by NF-κB down-regulation. Br J Pharmacol 2003.

Tumor Necrosis Factor-α Induced Cellular Stress on Trophoblastic Cells: NF-κB Signaling Could be a Potential Therapeutic Target

Year 2021, Volume: 80 Issue: 1, 9 - 14, 15.06.2021

Abstract

Objective: The development of the human placenta depends on proliferation and differentiation of trophoblastic cells. Deficiencies in trophoblastic functions are known to have a critical role in the progression of placental pathologies such as preeclampsia. Therefore, in this research, it was aimed to evaluate the responses of trophoblastic cells to tumor necrosis factor-α (TNF-α) mediated cellular stress.

Materials and Methods: In this study, the cellular stress model was set up by treating JAR cells with 100ng/ml TNF-α for 1, 6, 12 and 24 hour long periods. In this model, the effects of TNF-α on the proliferation capacity and apoptotic activity of JAR trophoblastic cells were investigated by immunocytochemistry. The nuclear and total expression levels of nuclear factor-κB (NF-κB) was evaluated with immunocytochemistry and Western blot, respectively.

Results: It was shown that 100 ng/ml TNF-α treated cells had a reduced proliferative capacity and increased apoptotic activity by immunocytochemical staining of PCNA and caspase-8 proteins respectively. In this respect, the NF-κB signaling pathway plays a critical role in TNF-α induced processes. So that, it was shown that the TNF-α treated group had increased nuclear and total NF-κB expressions compared to the untreated one.

Conclusion: Our findings showed that TNF-α has a significant role as a cellular stress source in JAR cells. TNF-α stimulated cellular response could be defined as decreased proliferative capacity, increased apoptotic activity and NF-κB signaling in JAR syncytiotrohoblastic cell lines. Therefore, investigation of TNF-α related cellular responses especially NF-κB signaling is further required for the understanding of the mechanism of placental pathologies which is crucial for the development of therapeutic approaches.

Supporting Institution

Research Fund of Istanbul University Project

Project Number

5737

References

  • 1. Knöfler M, Haider S, Saleh L, Pollheimer J, Gamage TKJB, James J. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci 2019;76:3479–96.
  • 2. Schoots MH, Gordijn SJ, Scherjon SA, van Goor H, Hillebrands J-L. Oxidative stress in placental pathology. Placenta 2018;69:153–61.
  • 3. Otun HA, Lash GE, Innes BA, Bulmer JN, Naruse K, Hannon T, et al. Effect of tumour necrosis factor-α in combination with interferon-γ on first trimester extravillous trophoblast invasion. J Reprod Immunol 2011;88:1–11.
  • 4. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci 2018;19:1496.
  • 5. Schütze S, Wiegmann K, Machleidt T, Krönke M. TNF-induced activation of NF-κB. Immunobiology 1995;193:193–203.
  • 6. Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol 2014;26:253–66.
  • 7. Wang L, Du F, Wang X. TNF-α induces two distinct caspase-8 activation pathways. Cell 2008;133(4):693-703.
  • 8. McCarty MF, O’Keefe JH, DiNicolantonio JJ. Pentoxifylline for vascular health: a brief review of the literature. Open Hear 2016;3:e000365.
  • 9. Samlaska CP, Winfield EA. Pentoxifylline. J Am Acad Dermatol 1994;30:603–21.
  • 10. Chen HL, Yang Y, Hu XL, Yelavarthi KK, Fishback JL, Hunt JS. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am J Pathol 1991;139(2):327-335..
  • 11. Guzel E, Basar M, Ocak N, Arici A, Kayisli UA. Bidirectional interaction between unfolded-protein-response key protein HSPA5 and estrogen signaling in human endometrium. Biol Reprod 2011;85:121–7.
  • 12. Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O, et al. Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies? Placenta 2011;32:S4–16.
  • 13. Roberts JM, Gammill HS. Preeclampsia. Hypertension 2005;46:1243–9.
  • 14. Uzun M, Gencer M, Turkon H, Oztopuz RO, Demir U, Ovali MA. Effects of melatonin on blood pressure, oxidative stress and placental expressions of TNFα, IL-6, VEGF and sFlt-1 in RUPP rat model of preeclampsia. Arch Med Res 2017;48:592–8.
  • 15. Raghupathy R. Cytokines as key players in the pathophysiology of preeclampsia. Med Princ Pract 2013;22:8–19.
  • 16. Weel IC, Baergen RN, Romão-Veiga M, Borges VT, Ribeiro VR, Witkin SS, et al. Association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia. PLoS One 2016;11:e0157584.
  • 17. Qin ZH, Wang Y, Kikly KK, Sapp E, Kegel KB, Aronin N, et al. Pro-caspase-8 is predominantly localized in mitochondria and released into cytoplasm upon apoptotic stimulation. J Biol Chem 2001.
  • 18. Boldin MP, Goncharov TM, Goltsev Y V., Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996;85:803–815.
  • 19. Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 1996;85:817–827.
  • 20. Collins JA, Schandl CA, Young KK, Vesely J, Willingham MC. Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem 1997;45(7):923-934.
  • 21. Albensi BC. What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion? Front Cell Dev Biol 2019;7.
  • 22. Durand JK, Baldwin AS. Targeting IKK and NF-κB for therapy. Adv Protein Chem Struct Biol 2017, p. 77–115.
  • 23. Kniss DA, Rovin B, Fertel RH, Zimmerman PD. Blockade NF-κB activation prohibits TNF-α-induced cyclooxygenase-2 gene expression in ED27 trophoblast-like cells. Placenta 2001.
  • 24. Armistead B, Kadam L, Drewlo S, Kohan-Ghadr HR. The role of NFκB in healthy and preeclamptic placenta: Trophoblasts in the spotlight. Int J Mol Sci 2020.
  • 25. Ciuffetti G, Mercuri M, Ott C, Lombardini R, Paltriccia R, Lupattelli G, et al. Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease. Eur J Clin Pharmacol 1991;41:511–5.
  • 26. Hendawy N. Pentoxifylline attenuates cytokine stress and Fas system in syngeneic liver proteins induced experimental autoimmune hepatitis. Biomed Pharmacother 2017;92:316–23.
  • 27. Muchhala SK, Benzeroual KE. Pentoxifylline suppressed LPS-induced inflammatory and apoptotic signaling in neuronal cells. Adv Biosci Biotechnol 2012;03:731–9.
  • 28. Chen YM, Tu CJ, Hung KY, Wu KD, Tsai TJ, Hsieh BS. Inhibition by pentoxifylline of TNF-α-stimulated fractalkine production in vascular smooth muscle cells: Evidence for mediation by NF-κB down-regulation. Br J Pharmacol 2003.
There are 28 citations in total.

Details

Primary Language English
Journal Section Research Articles
Authors

Erengul Varolli This is me 0000-0002-0270-5069

Serbay Özkan 0000-0001-7854-4735

Burcu Biltekin This is me 0000-0002-8435-6797

Meral Koyutürk 0000-0002-0270-5069

Project Number 5737
Publication Date June 15, 2021
Submission Date October 14, 2020
Published in Issue Year 2021 Volume: 80 Issue: 1

Cite

AMA Varolli E, Özkan S, Biltekin B, Koyutürk M. Tumor Necrosis Factor-α Induced Cellular Stress on Trophoblastic Cells: NF-κB Signaling Could be a Potential Therapeutic Target. Eur J Biol. June 2021;80(1):9-14.