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Intracellular inflammatory signalling cascades in human monocytic cells on challenge with phytohemagglutinin and 2,4,6-trinitrophenol

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A Correction to this article was published on 09 December 2021

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Abstract

Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.

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References

  1. McCullough KC, Summerfield A (2005) Basic concepts of immune response and defense development. ILAR J 46(3):230–240. https://doi.org/10.1093/ilar.46.3.230

    Article  CAS  PubMed  Google Scholar 

  2. Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR (2018) Pattern recognition receptors and the host cell death molecular machinery. Front Immunol 9:1–19. https://doi.org/10.3389/fimmu.2018.02379

    Article  CAS  Google Scholar 

  3. Guermonprez P, Valladeau J, Zitvogel L, Théry C, Amigorena S (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu rev immunol 20(1):621–667. https://doi.org/10.1146/annurev.immunol.20.100301.064828

    Article  CAS  PubMed  Google Scholar 

  4. Movafagh A, Heydary H, Mortazavi-Tabatabaei SA, Azargashb E (2011) The significance application of indigenous phytohemagglutinin (PHA) mitogen on metaphase and cell culture procedure. Iran J Pharm Res 10(4):895–903

    CAS  PubMed  PubMed Central  Google Scholar 

  5. De Groote D, Zangerlé PF, Gevaert Y, Fassotte MF, Beguin Y, Noizat-Pirenne F, Pirenne J, Gathy R, Lopez M, Dehart I, Igot D (1992) Direct stimulation of cytokines (IL-1β, TNF-α, IL-6, IL-2, IFN-γ and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation. Cytokine 4(3):239–248. https://doi.org/10.1016/1043-4666(92)90062-v

    Article  PubMed  Google Scholar 

  6. Askari VR, Rahimi VB, Zargarani R, Ghodsi R, Boskabady M, Boskabady MH (2020) Anti-oxidant and anti-inflammatory effects of auraptene on phytohemagglutinin (PHA)-induced inflammation in human lymphocytes. Pharmacol Rep 73(1):154–162. https://doi.org/10.1007/s43440-020-00083-5

    Article  CAS  PubMed  Google Scholar 

  7. Kamimaki C, Kobayashi N, Hirata M, Somekawa K, Fukuda N, Kubo S, Katakura S, Teranishi S, Watanabe K, Horita N, Hara Y (2021) T-cell response to phytohemagglutinin in the interferon-γ release assay as a potential biomarker for the response to immune checkpoint inhibitors in patients with non-small cell lung cancer. Thorac Cancer 12(11):1726–1734. https://doi.org/10.1111/1759-7714.13978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Venulet J, Desperak-Naciαzek ANNA (1966) Liver function and pyrexia caused by a pyrogen from Escherichia coli, lysergic acid diethylamide and dinitrophenol. J Pharm Pharmacol 18(1):38–40. https://doi.org/10.1111/j.2042-7158.1966.tb07768.x

    Article  CAS  PubMed  Google Scholar 

  9. Liu S, Wang N, Chen P, Li X, Liu C (2013) Effect of Huanglianjiedu Tang on fever in rats induced by 2,4-dinitrophenol. J Tradit Chin Med 33(4):492–499. https://doi.org/10.1016/s0254-6272(13)60154-5

    Article  PubMed  Google Scholar 

  10. Mohanan PV, Banerjee S, Geetha CS (2011) Detection of pyrogenicity on medical grade polymer materials using rabbit pyrogen, LAL and ELISA method. J Pharm Biomed Anal 55(5):1170–1174. https://doi.org/10.1016/j.jpba.2011.04.005

    Article  CAS  PubMed  Google Scholar 

  11. Lai W, Guo J, Zheng N, Nie Y, Ye S, Tang D (2020) Selective determination of 2,4,6-trinitrophenol by using a novel carbon nanoparticles as a fluorescent probe in real sample. Anal Bioanal Chem 412(13):3083–3090. https://doi.org/10.1007/s00216-020-02558-z

    Article  CAS  PubMed  Google Scholar 

  12. Borenfreund E, Puerner JA (1985) Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24(2–3):119–124. https://doi.org/10.1016/0378-4274(85)90046-3

    Article  CAS  PubMed  Google Scholar 

  13. Xu W, Larbi A (2018) Immunity and inflammation: from Jekyll to Hyde. Exp Gerontol 107:98–101. https://doi.org/10.1016/j.exger.2017.11.018

    Article  CAS  PubMed  Google Scholar 

  14. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L (2018) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9(6):7204–7218. https://doi.org/10.18632/oncotarget.23208

    Article  PubMed  Google Scholar 

  15. Ren J, Shi J, Kakuda Y, Kim D, Xue SJ, Zhao M, Jiang Y (2008) Phytohemagglutinin isolectins extracted and purified from red kidney beans and its cytotoxicity on human H9 lymphoma cell line. Sep Purif Technol 63(1):122–128. https://doi.org/10.1016/j.seppur.2008.04.004

    Article  CAS  Google Scholar 

  16. Sunderman FW, Weidman FD, Batson OV (1945) Studies of the effects of ammonium picrate on man and certain experimental animals. J Ind Hyg Toxicol 27(9):241–248

    CAS  PubMed  Google Scholar 

  17. Weeks MH, Asaki A, Wade J, Bongiovanni R (1983) Health hazards associated with demilitarization products of ammonium picrate (Explosive D)--In 1983 jannaf safety and environmental protection subcommittee meeting. Army Environmental Hygiene Agency, Aberdeen Proving Ground, MD https://www.dtic.mil/DTICOnline/downloadPdf.search?collectionId=tems&docId=CPIAC-1983-0248M. Accessed Sept 2020

  18. Kuo WT, Ho YJ, Kuo SM, Lin FH, Tsai FJ, Chen YS, Dong GC, Yao CH (2011) Induction of the mitochondria apoptosis pathway by phytohemagglutinin 172 erythroagglutinating in human lung cancer cells. Ann Surg Oncol 18(3):848–856. https://doi.org/10.1245/s10434-010-1351-2

    Article  PubMed  Google Scholar 

  19. Aits S, Jäättelä M (2013) Lysosomal cell death at a glance. J Cell Sci 126(9):1905–1912. https://doi.org/10.1242/jcs.091181

    Article  CAS  PubMed  Google Scholar 

  20. Signorello MG, Ravera S, Leoncini G (2020) Lectin-induced oxidative stress in human platelets. Redox Biol 32:1–11. https://doi.org/10.1016/j.redox.2020.101456

    Article  CAS  Google Scholar 

  21. Karwaciak I, Gorzkiewicz M, Bartosz G, Pulaski L (2017) TLR2 activation induces antioxidant defence in human monocyte-macrophage cell line models. Oncotarget 8(33):54243–54264. https://doi.org/10.18632/oncotarget.17342

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kochubei TO, Maksymchuk OV, Piven OO, Lukash LL (2015) Isolectins of phytohemagglutinin are able to induce apoptosis in HEp-2 carcinoma cells in vitro. Exp Oncol 37(2):116–119

    Article  CAS  Google Scholar 

  23. Orrenius S, Nicotera P, Zhivotovsky B (2011) Cell death mechanisms and their implications in toxicology. Toxicol Sci 119(1):3–19. https://doi.org/10.1093/toxsci/kfq268

    Article  CAS  PubMed  Google Scholar 

  24. McConkey DJ, Hartzell P, Duddy SK, Hakansson H, Orrenius S (1988) 2,3,7,8-Tetrachlorodibenzo- p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science 242:256–259

    Article  CAS  Google Scholar 

  25. Fan J, Nishanian P, Breen EC, McDonald M, Fahey JL (1998) Cytokine gene expression in normal human lymphocytes in response to stimulation. Clin Diagn Lab Immunol 5(3):335–340. https://doi.org/10.1128/CDLI.5.3.335-340.1998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jeljeli M, Guérin-El Khourouj V, Pédron B, Gressens P, Sibony O, Sterkers G (2019) Ontogeny of cytokine responses to PHA from birth to adulthood. Pediatr Res 86(1):63–70. https://doi.org/10.1038/s41390-019-0383-y

    Article  CAS  PubMed  Google Scholar 

  27. Schroeter CH, Schaub B, Gold DR, Contreras PJ, Manrique O, Gillman MW, Weiss S, Palmer LJ, Perkins D, Finn PW (2004) Nuclear factor kappa B activation in human cord blood mononuclear cells. Pediatr Res 56(2):212–218. https://doi.org/10.1203/01.PDR.0000132850.33375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Seto M (2004) Genetic and epigenetic factors involved in B-cell lymphomagenesis. Cancer Sci 95(9):704–710. https://doi.org/10.1111/j.1349-7006.2004.tb03249.x

    Article  CAS  PubMed  Google Scholar 

  29. Lúdvíksson BR, Ehrhardt RO, Strober W (1997) TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice. J Immunol 159(7):3622-3628.174

    PubMed  Google Scholar 

  30. Hu S, Chen CW, Chen ST, Tsui KH, Tang TK, Cheng HT, Hwang GS, Yu JW, Li YC, Wang PS, Wang SW (2019) Inhibitory effect of berberineon interleukin-2 secretion from PHA-treated lymphocytic Jurkat cells. Int Immunopharmacol 66:267–273. https://doi.org/10.1016/j.intimp.2018.11.020

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to express their thanks to the Director and Head, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Trivandrum, Kerala, India, for their support and for providing the infrastructure to carry out this work. Prajitha thanks the Council of Scientific and Industrial Research, New Delhi, for the SRF Fellowship.

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  1. Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695012, India

    N. Prajitha & P. V. Mohanan

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  1. N. Prajitha
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Correspondence to P. V. Mohanan.

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Prajitha, N., Mohanan, P.V. Intracellular inflammatory signalling cascades in human monocytic cells on challenge with phytohemagglutinin and 2,4,6-trinitrophenol. Mol Cell Biochem 477, 395–414 (2022). https://doi.org/10.1007/s11010-021-04296-x

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