Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid against Brucella abortus 544

  • Reyes, Alisha Wehdnesday Bernardo (Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Banos, College) ;
  • Kim, Heejin (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Huy, Tran Xuan Ngoc (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Nguyen, Trang Thi (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Min, Wongi (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Lee, Dongho (College of Medicine, Inje University) ;
  • Hur, Jin (College of Veterinary Medicine, Chonbuk National University) ;
  • Lee, John Hwa (College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Suk (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
  • Received : 2022.07.13
  • Accepted : 2022.08.25
  • Published : 2022.09.28
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Abstract

This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M4N) and zileuton (ZIL), and thromboxane A2 (TXA2) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M4N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M4N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d post-infection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA2 or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A3B05048283).

References

  1. Jamil T, Khan AU, Saqib M, Hussain MH, Melzer F, Rehman A, et al. 2021. Animal and human brucellosis in Pakistan. Front. Public Health 9: 660508. https://doi.org/10.3389/fpubh.2021.660508
  2. Karlsson PA, Persson C, Akoko J, Bett B, Lundkvist A, Lindahl JF. 2021. Using a one health case-based investigation for improved control of brucellosis in Isiolo, Kenya. Front. Trop. Dis. 2: 711425. https://doi.org/10.3389/fitd.2021.711425
  3. Dadar M, Tiwari R, Sharun K, Dhama K. 2021. Importance of brucellosis control programs of livestock on the improvement of one health. Vet. Q. 41: 137-151. https://doi.org/10.1080/01652176.2021.1894501
  4. Revora V, Marchesini MI, Comerci DJ. 2020. Brucella abortus depends on L-serine biosynthesis for intracellular proliferation. Infect. Immun. 88: e00840.
  5. Pizarro-Cerda J, Moreno E, Gorvel JP. 2000. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect. 2: 829-835. https://doi.org/10.1016/S1286-4579(00)90368-X
  6. Tallima H, El Ridi R. 2018. Arachidonic acid: physiological roles and potential health benefits - A review. J. Adv. Res. 11: 33-41. https://doi.org/10.1016/j.jare.2017.11.004
  7. Wang B, Wu L, Chen J, Dong L, Chen C, Wen Z, et al. 2021. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduct. Target Ther. 6: 94. https://doi.org/10.1038/s41392-020-00443-w
  8. Vu SH, Reyes AWB, Huy TXN, Min W, Lee HJ, Kim HJ, et al. 2021. Prostaglandin I2 (PGI2) inhibits Brucella abortus internalization in macrophages via PGI2 receptor signaling, and its analogue affects immune response and disease outcome in mice. Dev. Comp. Immunol. 115: 103902. https://doi.org/10.1016/j.dci.2020.103902
  9. Samuelsson B. 1987. An elucidation of the arachidonic acid cascade. Drugs 33: 2-9. https://doi.org/10.2165/00003495-198700331-00003
  10. Merino-Ramos T, Jimenez de Oya N, Saiz JC, Martin-Acebes MA. 2017. Antiviral activity of nordihydroguaiaretic acid and its derivative tetra-o-methyl nordihydroguaiaretic acid against West Nile virus and Zika virus. Antimicrob. Agents Chemother. 61:e00376-17.
  11. Bell RL, Young PR, Albert D, Lanni C, Summers JB, Brooks DW, et al. 1992. The discovery and development of zileuton: an orally active 5-lipoxygenase inhibitor. Int. J. Immunopharmacol. 14: 505-510. https://doi.org/10.1016/0192-0561(92)90182-K
  12. Cunningham-Oakes E, Soren O, Moussa C, Rathor G, Liu Y, Coates A, et al. 2015. Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin-sensitive and resistant Staphylococcus aureus in vitro and in vivo. Front. Microbiol. 6: 1195. https://doi.org/10.3389/fmicb.2015.01195
  13. Shimano H. 2002. Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Vitam. Horm. 65: 167-194. https://doi.org/10.1016/S0083-6729(02)65064-2
  14. Bertolio R, Napoletano F, Mano M, Maurer-Stroh S, Fantuz M, Zannini A, et al. 2019. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat. Commun. 10: 1326. https://doi.org/10.1038/s41467-019-09152-7
  15. Chen J, Bian X, Yao X, Gong W, Hu J, Chen K, et al. 2006. Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells. Biochem. Biophys. Res. Commun. 342: 1368-1374. https://doi.org/10.1016/j.bbrc.2006.02.113
  16. Jiang Z, Zhou W, Guan S, Wang J, Liang Y. 2013. Contribution of SDF-1α/CXCR4 signaling to brain development and glioma progression. Neurosignals. 21: 240-258. https://doi.org/10.1159/000339091
  17. Reyes AWB, Arayan LT, Huy TXN, Vu SH, Kang CK, Min W, et al. 2019. Chemokine receptor 4 (CXCR4) blockade enhances resistance to bacterial internalization in RAW264.7 cells and AMD3100, a CXCR4 antagonist, attenuates susceptibility to Brucella abortus 544 infection in a murine model. Vet. Microbiol. 237: 108402. https://doi.org/10.1016/j.vetmic.2019.108402
  18. Reyes AWB, Huy TXN, Vu SH, Kang CK, Min W, Lee HJ, et al. 2021. Formyl peptide receptor 2 (FPR2) antagonism is a potential target for the prevention of Brucella abortus 544 infection. Immunobiol. 226: 152073. https://doi.org/10.1016/j.imbio.2021.152073
  19. Needleman P, Raz A, Ferrendelli JA, Minkes M. 1977. Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets. Proc. Natl. Acad. Sci. USA 74: 1716-1720. https://doi.org/10.1073/pnas.74.4.1716
  20. Donowitz M. 1985. Arachidonic acid metabolites and their role in inflammatory bowel disease. Gastroenterology 88: 580-587. https://doi.org/10.1016/0016-5085(85)90525-6
  21. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Freeman A, Showell HJ. 2002. Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler. Thromb. Vasc. Biol. 22: 443-449. https://doi.org/10.1161/hq0302.105593
  22. Grillo M, Blasco JM, Gorvel JP, Moriyon I, Moreno E. 2012. What have we learned from brucellosis in the mouse model? Vet. Res. 43: 29. https://doi.org/10.1186/1297-9716-43-29
  23. Roop RM 2nd, Gaines JM, Anderson ES, Caswell CC, Martin DW. 2009. Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host. Med. Microbiol. Immunol. 198: 221-238. https://doi.org/10.1007/s00430-009-0123-8
  24. Fahel JS, de Souza MB, Gomes MT, Corsetti PP, Carvalho NB, Marinho FA, et al. 2015. 5-Lipoxygenase negatively regulates Th1 response during Brucella abortus infection in mice. Infect. Immun. 83: 1210-1216. https://doi.org/10.1128/IAI.02592-14
  25. Gagnaire A, Gorvel L, Papadopoulos A, Von Bargen K, Mege JL, Gorvel JP. 2016. COX-2 Inhibition reduces Brucella bacterial burden in draining lymph nodes. Front. Microbiol. 7: 1987. https://doi.org/10.3389/fmicb.2016.01987
  26. Spellberg B, Edwards, Jr. JE. 2001. Type 1/Type 2 immunity in infectious diseases. Clin. Infect. Dis. 32: 76-102. https://doi.org/10.1086/317537
  27. Le Bel M, Brunet A, Gosselin J. 2014. Leukotriene B4, an endogenous stimulator of the innate immune response against pathogens. J. Innate Immun. 6: 159-168. https://doi.org/10.1159/000353694
  28. Saeki K, Yokomizo T. 2017. Identification, signaling, and functions of LTB4 receptors. Semin. Immunol. 33: 30-36. https://doi.org/10.1016/j.smim.2017.07.010
  29. Ishii Y, Saeki K, Liu M, Sasaki F, Koga T, Kitajima K, et al. 2016. Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins. FASEB J. 30: 933-947. https://doi.org/10.1096/fj.15-279653
  30. Macedo GC, Magnani DM, Carvalho NB, Bruna-Romero O, Gazzinelli RT, Oliveira SC. 2008. Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection. J. Immunol. 180: 1080-1087. https://doi.org/10.4049/jimmunol.180.2.1080
  31. Deshmane SL, Kremlev S, Amini S, Sawaya BE. 2009. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res. 29: 313-326. https://doi.org/10.1089/jir.2008.0027
  32. Kutlu M, Ergin C, Sen-Turk N, Sayin-Kutlu S, Zorbozan O, Akalin S, et al. 2015. Acute Brucella melitensis M16 infection model in mice treated with tumor necrosis factor-alpha inhibitors. J. Infect. Developing Countries 9: 141-148. https://doi.org/10.3855/jidc.5155
  33. Pasquali P, Adone R, Gasbarre LC, Pistoia C, Ciuchini F. 2002. Effect of exogenous interleukin-18 (IL-18) and IL-12 in the course of Brucella abortus 2308 infection in mice. Clin. Diagn. Lab. Immunol. 9: 491-492.
  34. Kim S, Lee DS, Watanabe K, Furuoka H, Suzuki H, Watarai M. 2005. Interferon-gamma promotes abortion due to Brucella infection in pregnant mice. BMC Microbiol. 5: 22. https://doi.org/10.1186/1471-2180-5-22
  35. Haraguchi S, Day NK, Nelson RP Jr, Emmanuel P, Duplantier JE, Christodoulou CS, et al. 1998. Interleukin 12 deficiency associated with recurrent infections. Proc. Natl. Acad. Sci. USA 95: 13125-13129. https://doi.org/10.1073/pnas.95.22.13125
  36. Hodge-Dufour J, Marino MW, Horton MR, Jungbluth A, Burdick MD, Strieter RM, et al. 1998. Inhibition of interferon gamma induced interleukin 12 production: a potential mechanism for the anti-inflammatory activities of tumor necrosis factor. Proc. Natl. Acad. Sci. USA 95: 13806-13811. https://doi.org/10.1073/pnas.95.23.13806
  37. Xavier M, Winter, Atluri V, Godinez I, Silva T, Barton G, et al. 2012. Anti-inflammatory role of IL-10 producing macrophages during early Brucella abortus infection. J. Immunol. 188: 117-120.
  38. Corsetti PP, de Almeida LA, Carvalho NB, Azevedo V, Silva TM, Teixeira HC, et al. 2013. Lack of endogenous IL-10 enhances production of proinflammatory cytokines and leads to Brucella abortus clearance in mice. PLoS One 8: e74729. https://doi.org/10.1371/journal.pone.0074729