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Anti-inflammatory effect of chrysin on RAW 264.7 mouse macrophages induced with polyinosinic-polycytidylic acid

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Abstract

Chrysin (5,7-Dihydroxyflavone) is an active flavonoid isolated from Scutellariae Radix which has been used to treat pneumonia, laryngopharyngitis, jaundice, shigellosis, and breast mass in Korea, China, and Japan. Chrysin has been already reported to inhibit inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharideinduced macrophages. However, the effect of chrysin on virus-induced macrophages is not fully reported. In this study, the anti-inflammatory effect of chrysin on doublestranded RNA (dsRNA)-induced macrophages was examined. Production of Nitric oxide (NO), various cytokines, as well as calcium release and mRNA expression of CHOP and Fas in dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 mouse macrophages were evaluated. Chrysin restored the cell viability in dsRNA [polyinosinicpolycytidylic acid]-induced RAW 264.7 mouse macrophages at concentrations of up to 50 μM. Chrysin significantly inhibited the production of NO, IL-1α, IL-1β, IL-6, IL-10, IP-10, G-CSF, GM-CSF, LIF, LIX/CXCL5, MCP-1, MCSF, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, and VEGF as well as calcium release and mRNA expression of CHOP and Fas in dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 mouse macrophages (P< 0.05). These data suggest that chrysin has anti-inflammatory properties related with its inhibition of nitric oxide, cytokines, chemokines, and growth factors in dsRNA-induced macrophages via the ER stress-CHOP pathway.

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References

  1. Chuang, H. N., J. Y. Wang, J. H. Chiu, T. H. Tsai, S. F. Yeh, S. L. Fu, W. Y. Lui, and C. W. Wu (2005) Enhancing effects of Scutellaria baicalensis and some of its constituents on TGF-beta1 gene expression in RAW 264.7 murine macrophage cell line. Planta Med. 71: 440–445.

    Article  CAS  Google Scholar 

  2. Kellis, J. T., Jr and L. E. Vickery (1984) Inhibition of human estrogen synthetase (aromatase) by flavones. Sci. 225: 1032–1034.

    Article  CAS  Google Scholar 

  3. Woo, K. J., Y. J. Jeong, H. Inoue, J. W. Park, and T. K. Kwon (2005) Chrysin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression through the inhibition of nuclear factor for IL-6 (NF-IL6) DNA-binding activity. FEBS Lett. 579: 705–711.

    Article  CAS  Google Scholar 

  4. Bauernfeind, F. and V. Hornung (2013) Of inflammasomes and pathogens—sensing of microbes by the inflammasome. EMBO Mol. Med. 5: 814–826.

    Article  CAS  Google Scholar 

  5. Hoarau, J. J., P. Krejbich-Trotot, M. C. Jaffar-Bandjee, T. Das, G. V. Thon-Hon, S. Kumar, J. W. Neal, and P. Gasque (2011) Activation and control of CNS innate immune responses in health and diseases: A balancing act finely tuned by neuroimmune regulators (NIReg). CNS Neurol. Disord. Drug Targets. 10: 25–43.

    Article  CAS  Google Scholar 

  6. dos Santos, G., M. A. Kutuzov, and K. M. Ridge (2012) The inflammasome in lung diseases. Am. J. Physiol. Lung Cell. Mol. Physiol. 303: L627–633.

    Article  CAS  Google Scholar 

  7. Im, H. and A. J. Ammit (2014) The NLRP3 inflammasome: Role in airway inflammation. Clin. Exp. Allergy. 44: 160–172.

    Article  CAS  Google Scholar 

  8. Liu, H. D., W. Li, Z. R. Chen, Y. C. Hu, D. D. Zhang, W. Shen, M. L. Zhou, L. Zhu, and C. H. Hang (2013) Expression of the NLRP3 inflammasome in cerebral cortex after traumatic brain injury in a rat model. Neurochem. Res. 38: 2072–2083.

    Article  CAS  Google Scholar 

  9. Skeldon, A. M., M. Faraj, and M. Saleh (2014) Caspases and inflammasomes in metabolic inflammation. Immunol. Cell Biol. 92: 304–313.

    Article  CAS  Google Scholar 

  10. Medina, E. A., I. R. Morris, and M. T. Berton (2010) Phosphatidylinositol 3-kinase activation attenuates the TLR2-mediated macrophage proinflammatory cytokine response to Francisella tularensis live vaccine strain. J. Immunol. 185: 7562–7572.

    Article  CAS  Google Scholar 

  11. Hernansanz-Agustin, P., A. Izquierdo-Alvarez, A. Garcia-Ortiz, S. Ibiza, J. M. Serrador, and A. Martinez-Ruiz (2013) Nitrosothiols in the immune system: Signaling and protection. Antioxid. Redox Signal. 18: 288–308.

    Article  CAS  Google Scholar 

  12. O'Shea, J. J., A. Ma, and P. Lipsky (2002) Cytokines and autoimmunity. Nat. Rev. Immunol. 2: 37–45.

    Article  CAS  Google Scholar 

  13. Schulte, W., J. Bernhagen, and R. Bucala (2013) Cytokines in sepsis: Potent immunoregulators and potential therapeutic targets—an updated view. Mediators Inflamm. 2013: 165974.

    Article  CAS  Google Scholar 

  14. Hasan, M., C. Ruksznis, Y. Wang, and C. A. Leifer (2011) Antimicrobial peptides inhibit polyinosinic-polycytidylic acid-induced immune responses. J. Immunol. 187: 5653–5659.

    Article  CAS  Google Scholar 

  15. Rintahaka, J., N. Lietzen, T. Ohman, T. A. Nyman, and S. Matikainen (2011) Recognition of cytoplasmic RNA results in cathepsin-dependent inflammasome activation and apoptosis in human macrophages. J. Immunol. 186: 3085–3092.

    Article  CAS  Google Scholar 

  16. Yoon, S. B., Y. J. Lee, S. K. Park, H. C. Kim, H. Bae, H. M. Kim, S. G. Ko, H. Y. Choi, M. S. Oh, and W. Park (2009) Anti-inflammatory effects of Scutellaria baicalensis water extract on LPSactivated RAW 264.7 macrophages. J. Ethnopharmacol. 125: 286–290.

    Article  Google Scholar 

  17. Yuk, S. S., E. M. Lim, J. Y. Lee, Y. J. Lee, Y. S. Kim, T. H. Lee, S. K. Park, H. Bae, H. M. Kim, S. G. Ko, M. S. Oh, and W. Park (2010) Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide-activated RAW264.7 macrophages. Phytother. Res. 24: 1781–1787.

    Article  CAS  Google Scholar 

  18. Flagella, M., S. Bui, Z. Zheng, C. T. Nguyen, A. Zhang, L. Pastor, Y. Ma, W. Yang, K. L. Crawford, G. K. McMaster, F. Witney, and Y. Luo (2006) A multiplex branched DNA assay for parallel quantitative gene expression profiling. Anal. Biochem. 352: 50–60.

    Article  CAS  Google Scholar 

  19. Lin, K. M., W. Hu, T. D. Troutman, M. Jennings, T. Brewer, X. Li, S. Nanda, P. Cohen, J. A. Thomas, and C. Pasare (2014) IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation. Proc. Natl. Acad. Sci. U. S. A. 111: 775–780.

    Article  CAS  Google Scholar 

  20. Spite, M., L. V. Norling, L. Summers, R. Yang, D. Cooper, N. A. Petasis, R. J. Flower, M. Perretti, and C. N. Serhan (2009) Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Natur. 461: 1287–1291.

    Article  CAS  Google Scholar 

  21. Lee, J. Y. and W. Park (2011) Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinicpolycytidylic acid. Molecule. 16: 7132–7142.

    Article  CAS  Google Scholar 

  22. Nathan, C. F. and J. B. Hibbs Jr (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol. 3: 65–70.

    Article  CAS  Google Scholar 

  23. Gotoh, T., K. Terada, S. Oyadomari, and M. Mori (2004) hsp70-DnaJ chaperone pair prevents nitric oxide-and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ. 11: 390–402.

    Article  CAS  Google Scholar 

  24. Burska, A., M. Boissinot, and F. Ponchel (2014) Cytokines as biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014: 545493.

    Google Scholar 

  25. Nakagawa, H., T. Tamura, Y. Mitsuda, Y. Goto, Y. Kamiya, T. Kondo, K. Wakai, and N. Hamajima (2014) Inverse correlation between serum interleukin-6 and iron levels among Japanese adults: A cross-sectional study. BMC Hematol. 14: 6-1839-14-6.

  26. Niebler, M., X. Qian, D. Hofler, V. Kogosov, J. Kaewprag, A. M. Kaufmann, R. Ly, G. Bohmer, R. Zawatzky, F. Rosl, and B. Rincon-Orozco (2013) Post-translational control of IL-1beta via the human papillomavirus type 16 E6 on coprotein: A novel mechanism of innate immune escape mediated by the E3-ubiquitin ligase E6-AP and p53. PLoS Pathog. 9: e1003536.

    Article  CAS  Google Scholar 

  27. Hu, Z., T. Murakami, K. Suzuki, H. Tamura, K. Kuwahara-Arai, T. Iba, and I. Nagaoka (2014) Antimicrobial cathelicidin peptide LL-37 inhibits the LPS/ATP-induced pyroptosis of macrophages by dual mechanism. PLoS One. 9: e85765.

    Article  CAS  Google Scholar 

  28. Ulloa, L. and K. J. Tracey (2005) The "cytokine profile": A code for sepsis. Trends Mol. Med. 11: 56–63.

    Article  CAS  Google Scholar 

  29. Sessler, C. N. and W. Shepherd (2002) New concepts in sepsis. Curr. Opin. Crit. Care. 8: 465–472.

    Article  Google Scholar 

  30. Maskrey, B. H., I. L. Megson, P. D. Whitfield, and A. G. Rossi (2011) Mechanisms of resolution of inflammation: A focus on cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 31: 1001–1006.

    Article  CAS  Google Scholar 

  31. Tracey, D., L. Klareskog, E. H. Sasso, J. G. Salfeld, and P. P. Tak (2008) Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacol. Ther. 117: 244–279.

    Article  CAS  Google Scholar 

  32. Present, D. H., P. Rutgeerts, S. Targan, S. B. Hanauer, L. Mayer, R. A. van Hogezand, D. K. Podolsky, B. E. Sands, T. Braakman, K. L. DeWoody, T. F. Schaible, and S. J. van Deventer (1999) Infliximab for the treatment of fistulas in patients with Crohn's disease. N. Engl. J. Med. 340: 1398–1405.

    Article  CAS  Google Scholar 

  33. Ballara, S., P. C. Taylor, P. Reusch, D. Marme, M. Feldmann, R. N. Maini, and E. M. Paleolog (2001) Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 44: 2055–2064.

    Article  CAS  Google Scholar 

  34. Ruddy, M. J., F. Shen, J. B. Smith, A. Sharma, and S. L. Gaffen (2004) Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: Implications for inflammation and neutrophil recruitment. J. Leukoc. Biol. 76: 135–144.

    Article  CAS  Google Scholar 

  35. Srivastava, M., S. Jung, J. Wilhelm, L. Fink, F. Buhling, T. Welte, R. M. Bohle, W. Seeger, J. Lohmeyer, and U. A. Maus (2005) The inflammatory versus constitutive trafficking of mononuclear phagocytes into the alveolar space of mice is associated with drastic changes in their gene expression profiles. J. Immunol. 175: 1884–1893.

    Article  CAS  Google Scholar 

  36. Wareing, M. D., A. B. Lyon, B. Lu, C. Gerard, and S. R. Sarawar (2004) Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. J. Leukoc. Biol. 76: 886–895.

    Article  CAS  Google Scholar 

  37. Dace, D. S., A. A. Khan, J. L. Stark, J. Kelly, A. H. Cross, and R. S. Apte (2009) Interleukin-10 overexpression promotes Fasligand-dependent chronic macrophage-mediated demyelinating polyneuropathy. PLoS One. 4: e7121.

    Article  CAS  Google Scholar 

  38. Schwantes, E. A., D. M. Manthei, L. C. Denlinger, M. D. Evans, J. E. Gern, N. N. Jarjour, and S. K. Mathur (2014) Interferon gene expression in sputum cells correlates with the Asthma Index Score during virus-induced exacerbations. Clin. Exp. Allerg. 44: 813–821.

    Article  CAS  Google Scholar 

  39. Hu, C. P., J. T. Feng, Y. L. Tang, J. Q. Zhu, M. J. Lin, and M. E. Yu (2006) LIF upregulates expression of NK-1R in NHBE cells. Mediators Inflamm. 2006: 84829.

    Article  CAS  Google Scholar 

  40. Gotoh, T., S. Oyadomari, K. Mori, and M. Mori (2002) Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP. J. Biol. Chem. 277: 12343–12350.

    Article  CAS  Google Scholar 

  41. Timmins, J. M., L. Ozcan, T. A. Seimon, G. Li, C. Malagelada, J. Backs, T. Backs, R. Bassel-Duby, E. N. Olson, M. E. Anderson, and I. Tabas (2009) Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J. Clin. Invest. 119: 2925–2941.

    Article  CAS  Google Scholar 

  42. Tabas, I., T. Seimon, J. Timmins, G. Li, and W. Lim (2009) Macrophage apoptosis in advanced atherosclerosis. Ann. N. Y. Acad. Sci. 1173 Suppl 1: E40-5.

    Google Scholar 

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  1. Department of Pathology, College of Korean Medicine, Gachon University, Seongnam, 461-701, Korea

    Ji Young Lee & Wansu Park

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  1. Ji Young Lee
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  2. Wansu Park
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Correspondence to Wansu Park.

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Lee, J.Y., Park, W. Anti-inflammatory effect of chrysin on RAW 264.7 mouse macrophages induced with polyinosinic-polycytidylic acid. Biotechnol Bioproc E 20, 1026–1034 (2015). https://doi.org/10.1007/s12257-015-0416-2

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