LPS induces inflammatory chemokines via TLR-4 signalling and enhances the Warburg Effect in THP-1 cells


Autoři: Philemon Ubanako aff001;  Ntombikayise Xelwa aff001;  Monde Ntwasa aff002
Působiště autorů: School of Molecular & Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa aff001;  Department of Life & Consumer Sciences, University of South Africa, Florida, Johannesburg, Republic of South Africa aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222614

Souhrn

The Warburg Effect has emerged as a potential drug target because, in some cancer cell lines, it is sufficient to subvert it in order to kill cancer cells. It has also been shown that the Warburg Effect occurs in innate immune cells upon infection. Innate immune cells play critical roles in the tumour microenvironment but the Warburg Effect is not fully understood in monocytes. Furthermore, it is important to understand the impact of infections on key players in the tumour microenvironment because inflammatory conditions often precede carcinogenesis and mutated oncogenes induce inflammation. We investigated the metabolic programme in the acute monocytic leukaemia cell line, THP-1 in the presence and absence of lipopolysaccharide, mimicking bacterial infections. We found that stimulation of THP-1 cells by LPS induces a subset of pro-inflammatory chemokines and enhances the Warburg Effect. Surprisingly, perturbation of the Warburg Effect in these cells does not lead to cell death in contrast to what was observed in non-myeloid cancer cell lines in a previous study. These findings indicate that the Warburg Effect and inflammation are activated by bacterial lipopolysaccharide and may have a profound influence on the microenvironment.

Klíčová slova:

Cell cycle and cell division – Cytokines – Chemokines – Monocytes – Pyruvate – Warburg effect – Cell metabolism – Polymyxins


Zdroje

1. Warburg O, Wind F, Negelein E (1927). The metabolism of tumors in the body T. The Journal of General Physiology 8: 519–530. doi: 10.1085/jgp.8.6.519 19872213

2. Hanahan D, Weinberg Robert A (2011). Hallmarks of cancer: The next generation. Cell 144: 646–674. doi: 10.1016/j.cell.2011.02.013 21376230

3. McGettrick AF, O'Neill LAJ (2013). How metabolism generates signals during innate immunity and inflammation. Journal of Biological Chemistry 288: 22893–22898. doi: 10.1074/jbc.R113.486464 23798679

4. Palsson-McDermott EM, O’Neill LAJ (2013). The Warburg effect then and now: from cancer to inflammatory diseases. BioEssays 35.

5. Monchusi B, Ntwasa M (2017). Methyl pyruvate protects a normal lung fibroblast cell line from irinotecan-induced cell death: Potential use as adjunctive to chemotherapy. PLoS One 12(8): e0182789. doi: 10.1371/journal.pone.0182789 28797070

6. Fox CJ, Hammerman PS, Thompson CB (2005). Fuel feeds function: energy metabolism and the T-cell response. Nature Reviews Immunology 5: 844. doi: 10.1038/nri1710 16239903

7. Pearce Erika L, Pearce Edward J (2013). Metabolic pathways in immune cell activation and quiescence. Immunity 38: 633–643. doi: 10.1016/j.immuni.2013.04.005 23601682

8. Kominsky DJ, Campbell EL, Colgan SP (2010). Metabolic shifts in immunity and inflammation. The Journal of Immunology 184: 4062. doi: 10.4049/jimmunol.0903002 20368286

9. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. (2011). HIF1a–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of T<sub>H</sub>17 and T<sub>reg</sub> cells. The Journal of Cell Biology 194: i1.

10. Kelly B, O'Neill LAJ (2015). Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Research 25: 771. doi: 10.1038/cr.2015.68 26045163

11. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, et al. (2010). Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115: 4742–4749. doi: 10.1182/blood-2009-10-249540 20351312

12. Bosshart H, Heinzelmann M (2016). THP-1 cells as a model for human monocytes. Annals of Translational Medicine 4: 438. doi: 10.21037/atm.2016.08.53 27942529

13. Chanput W, Mes J, Vreeburg RAM, Savelkoul HFJ, Wichers HJ (2010). Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds. Food Funct 1: 254–261. doi: 10.1039/c0fo00113a 21776474

14. Raulien N, Friedrich K, Strobel S, Rubner S, Baumann S, von Bergen M, et al. (2017). Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes. Frontiers in Immunology 8.

15. Parkin DM (2006). The global health burden of infection-associated cancers in the year 2002. International Journal of Cancer 118: 3030–3044. doi: 10.1002/ijc.21731 16404738

16. Coussens LM, Werb Z (2002). Inflammation and cancer. Nature 420: 860. doi: 10.1038/nature01322 12490959

17. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009). Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30: 1073–1081. doi: 10.1093/carcin/bgp127 19468060

18. Dranoff G (2004). Cytokines in cancer pathogenesis and cancer therapy. Nature Reviews Cancer 4: 11. doi: 10.1038/nrc1252 14708024

19. Jones VS, Huang R-Y, Chen L-P, Chen Z-S, Fu L, Huang R-P (2016). Cytokines in cancer drug resistance: Cues to new therapeutic strategies. Biochimica et Biophysica Acta (BBA)—Reviews on Cancer 1865: 255–265.

20. Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA (2014). Chronic inflammation and cytokines in the tumor microenvironment. Journal of Immunology Research 2014: 19.

21. Rodríguez-Prados J-C, Través PG, Cuenca J, Rico D, Aragonés J, Martín-Sanz P, et al. (2010). Substrate fate in activated macrophages: A comparison between innate, classic, and alternative activation. The Journal of Immunology.

22. Oda T, Hirota K, Nishi K, Takabuchi S, Oda S, Yamada H, et al. (2006). Activation of hypoxia-inducible factor 1 during macrophage differentiation. American Journal of Physiology-Cell Physiology 291: C104–C113. doi: 10.1152/ajpcell.00614.2005 16481368

23. Nishi Kenichiro, Oda Tomoyuki, Takabuchi Satoshi, Oda Seiko, Fukuda Kazuhiko, Adachi Takehiko, et al. (2008). LPS induces hypoxia-inducible factor 1 activation in macrophage-differentiated cells in a reactive oxygen species–dependent manner. Antioxidants & Redox Signaling 10: 983–995.

24. Mostafavi S, Ray D, Warde-Farley D, Grouios C, Morris Q (2008). GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome Biology 9: S4.

25. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. (2010). The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Research 38: W214–W220. doi: 10.1093/nar/gkq537 20576703

26. Lemasters JJ, Qian T, He L, Kim J-S, Elmore SP, Cascio WE, et al. (2002). Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxidants & Redox Signaling 4: 769–781.

27. Sterling T, Irwin JJ (2015). ZINC 15 –Ligand discovery for everyone. Journal of Chemical Information and Modeling 55: 2324–2337. doi: 10.1021/acs.jcim.5b00559 26479676

28. Wong AK, Park CY, Greene CS, Bongo LA, Guan Y, Troyanskaya OG (2012). IMP: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks. Nucleic Acids Research 40: W484–W490. doi: 10.1093/nar/gks458 22684505

29. Haase M, Fitze G (2016). HSP90AB1: Helping the good and the bad. Gene 575: 171–186. doi: 10.1016/j.gene.2015.08.063 26358502

30. Karsan A, Yee E, Kaushansky K, Harlan JM (1996). Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells. Blood 87: 3089. 8605321

31. Song HY, Rothe M, Goeddel DV (1996). The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 93: 6721–6725. doi: 10.1073/pnas.93.13.6721 8692885

32. Ha T-K, Chi S-G (2012). CAV1/caveolin 1 enhances aerobic glycolysis in colon cancer cells via activation of SLC2A3/GLUT3 transcription. Autophagy 8: 1684–1685. doi: 10.4161/auto.21487 22874559

33. Wu X, Freeze HH (2002). GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative splice forms. Genomics 80: 553–557. doi: 10.1006/geno.2002.7010 12504846

34. Seuter S, Pehkonen P, Heikkinen S, Carlberg C (2013). The gene for the transcription factor BHLHE40/DEC1/stra13 is a dynamically regulated primary target of the vitamin D receptor. The Journal of Steroid Biochemistry and Molecular Biology 136: 62–67. doi: 10.1016/j.jsbmb.2012.11.011 23220548

35. Wong LYF, Cheung BMY, Li Y-Y, Tang F (2005). Adrenomedullin is both proinflammatory and antiinflammatory: Its effects on gene expression and secretion of cytokines and macrophage Migration Inhibitory Factor in NR8383 macrophage cell line. Endocrinology 146: 1321–1327. doi: 10.1210/en.2004-1080 15576460

36. Zhang D, Chen L, Li S, Gu Z, Yan J (2008). Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces IL-1β, TNF-α and IL-6 production by THP-1 cells in a way different from that of Escherichia coli LPS. Innate Immunity 14: 99–107. doi: 10.1177/1753425907088244 18713726

37. Zhang FX, Kirschning CJ, Mancinelli R, Xu X-P, Jin Y, Faure E, et al. (1999). Bacterial lipopolysaccharide activates Nuclear Factor-κB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. Journal of Biological Chemistry 274: 7611–7614. doi: 10.1074/jbc.274.12.7611 10075645

38. Vadiveloo PK, Keramidaris E, Morrison WA, Stewart AG (2001). Lipopolysaccharide-induced cell cycle arrest in macrophages occurs independently of nitric oxide synthase II induction. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research 1539: 140–146.

39. Vadiveloo PK, Vairo G, Novak U, Royston AK, Whitty G, Filonzi EL, et al. (1996). Differential regulation of cell cycle machinery by various antiproliferative agents is linked to macrophage arrest at distinct G1 checkpoints. Oncogene 13: 599–608. 8760301

40. Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH (1992). Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proceedings of the National Academy of Sciences 89: 6711.

41. Graña X, Reddy E (1995). Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11: 211–219. 7624138

42. Birkenmeier G, Hemdan NYA, Kurz S, Bigl M, Pieroh P, Debebe T, et al. (2016). Ethyl pyruvate combats human leukemia cells but spares normal blood cells. PLoS ONE 11: e0161571. doi: 10.1371/journal.pone.0161571 27579985

43. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004). The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 25: 677–686. doi: 10.1016/j.it.2004.09.015 15530839

44. Vogler M (2011). BCL2A1: the underdog in the BCL2 family. Cell Death and Differentiation 19: 67. doi: 10.1038/cdd.2011.158 22075983

45. Semenza GL (2001). Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends in Molecular Medicine 7: 345–350. 11516994


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2019 Číslo 9

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