1887

Abstract

Japanese encephalitis virus (JEV) infection generates a rapid inflammatory response including peripheral neutrophil leucocytosis and infiltration of neutrophils into extraneural tissue. The level of inflammation correlates well with the clinical outcome in Japanese encephalitis patients. Non-steroidal anti-inflammatory drugs (NSAIDs), used medicinally for their analgesic and anti-inflammatory properties, are being considered for prevention of cardiovascular disease and cancer, as well as for treatment of human immunodeficiency virus infection. Apart from their ability to inhibit prostaglandin synthesis, the mechanisms underlying the beneficial therapeutic effects are largely unknown. We used aspirin, indomethacin and sodium salicylate to study the role of NSAIDs in JEV propagation . We found that NSAIDs suppressed JEV propagation in neuronal and non-neuronal cells. Blockade of cyclooxygenase activity by NSAIDs caused decreased production of free radicals and prostaglandins. However, these pharmacological alterations did not seem to correlate well with the antiviral effects. When cells were treated with the mitogen-activated protein kinase (MAPK) inhibitors PD 98059 and SB 203580, salicylate lost its antiviral effect. The activation of MAPK by anisomycin mimicked the action of salicylate in suppressing JEV-induced cytotoxicity. The decreased phosphorylation of extracellular signal-regulated kinase (ERK) was induced by JEV infection and the decrease in ERK was reversed by salicylate. Our data suggest that the signalling pathways of MAPK play a role in the antiviral action of salicylate.

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2002-08-01
2024-04-19
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References

  1. Axelroid J., Burch R. M., Jelsema C. L. 1988; Receptor-mediated activation of phospholipase A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers. Trends in Neuroscience 11:117–123
    [Google Scholar]
  2. Bitko V., Velazquez A., Yang L., Yang Y. C., Barik S. 1997; Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kappaB and is inhibited by sodium salicylate and aspirin. Virology 232:369–378
    [Google Scholar]
  3. Chambers T. J., Hahn C. S., Galler R., Rice C. M. 1990; Flavivirus genome organization, expression, and replication. Annual Review of Microbiology 44:649–688
    [Google Scholar]
  4. Chang M. F., Chen C. J., Chang S. C. 1994; Mutational analysis of delta antigen: effect on assembly and replication of hepatitis delta virus. Journal of Virology 68:646–653
    [Google Scholar]
  5. Chaturvedi U. C., Mathur A., Tandon P., Natu S. M., Rajvanshi S., Tandon H. O. 1979; Variable effect on peripheral blood leucocytes during JE virus infection of man. Clinical and Experimental Immunology 38:492–498
    [Google Scholar]
  6. Chen C. J., Kuo M. D., Chien L. J., Hsu S. L., Wang Y. M., Lin J. H. 1997; RNA–protein interactions: involvement of NS3, NS5, and 3’ noncoding regions of Japanese encephalitis virus genomic RNA. Journal of Virology 71:3466–3473
    [Google Scholar]
  7. Chen N., Warner J. L., Reiss C. S. 2000; NSAID treatment suppresses VSV propagation in mouse CNS. Virology 276:44–51
    [Google Scholar]
  8. Cirino G. 1998; Multiple controls in inflammation, extracellular and intracellular phospholipase A2, inducible and constitutive cyclooxygenase, and inducible nitric oxide synthase. Biochemical Pharmacology 55:105–111
    [Google Scholar]
  9. Cossarizza A., Franceschi C., Monti D., Salvioli S., Bellesia E., Rivabene R., Biondo L., Rainaldi G., Tinari A., Malorni W. 1995; Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitrochondria. Experimental Cell Research 220:232–240
    [Google Scholar]
  10. Gilman A. G., Rall T. W., Nies A. S., Taylor P. 1990 The Pharmacological Basis of Therapeutics , 8th edn. Elmsford, NY: Pergamon Press;
    [Google Scholar]
  11. Glaser K. B. 1995; Regulation of phospholipase A2 enzymes: selective inhibitors and their pharmacological potential. Advances in Pharmacology 32:31–66
    [Google Scholar]
  12. Grilli M., Pizzi M., Memo M., Spano P. 1996; Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science 274:1383–1385
    [Google Scholar]
  13. Huang R. T., Dietsch E. 1988; Anti-influenza viral activity of aspirin in cell culture. New England Journal of Medicine 319:797
    [Google Scholar]
  14. Jan J. T., Chen B. H., Ma S. H., Liu C. I., Tsai H. P., Wu H. C., Jiang S. Y., Yang K. D., Shaio M. F. 2000; Potential Dengue virus-triggered apoptotic pathway in human neuroblastoma cells: arachidonic acid, superoxide anion, and NF- κB are sequentially involved. Journal of Virology 74:8680–8691
    [Google Scholar]
  15. Kalgutkar A. S., Crews B. C., Rowlinson S. W., Garner C., Seibert K., Marnett L. J. 1998; Aspirin-like molecules that covalently inactivate cyclooxygenase-21211. Science 280:1268–1270
    [Google Scholar]
  16. Karin M. 1998; Mitogen-activated protein kinase cascades as regulators of stress responses. Annals of the New York Academy of Sciences 851:139–146
    [Google Scholar]
  17. Khanna N., Agnihotri M., Mathur A., Chaturvedi U. C. 1991; Neutrophil chemotactic factor produced by Japanese encephalitis virus stimulated macrophages. Clinical and Experimental Immunology 86:299–303
    [Google Scholar]
  18. Kumar R., Mathur A., Kumar A., Sethi G. D., Sharma S., Chaturvedi U. C. 1990; Virological investigations of acute encephalopathy in India. Archives of Disease in Childhood 65:1227–1230
    [Google Scholar]
  19. Liao C. L., Lin Y. L., Wu B. C., Tsao C. H., Wang M. C., Liu C. I., Huang Y. L., Chen J. H., Wang J. P., Chen L. K. 2001; Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation. Journal of Virology 75:7828–7839
    [Google Scholar]
  20. Lin Y. L., Huang Y. L., Ma S. H., Yeh C. T., Chiou S. Y., Chen L. K., Liao C. L. 1997; Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication. Journal of Virology 71:5227–5235
    [Google Scholar]
  21. Lowy R. J., Dimitrov D. S. 1997; Characterization of influenza virus-induced death of J774.1 macrophages. Experimental Cell Research 234:249–258
    [Google Scholar]
  22. Mathur A., Bharadwaj M., Kulshreshtha R., Rawat S., Jain A., Chaturvedi U. C. 1988; Immunopathological study of spleen during Japanese encephalitis virus infection in mice. British Journal of Experimental Pathology 69:423–432
    [Google Scholar]
  23. Oh-hashi K., Maruyama W., Yi H., Takahashi T., Naoi M., Isobe K. 1999; Mitogen-activated protein kinase pathway mediates peroxynitrite-induced apoptosis in human dopaminergic neuroblastoma SH-SY5Y cells. Biochemical and Biophysical Research Communications 263:504–509
    [Google Scholar]
  24. Patrignani P. 2000; Nonsteroidal anti-inflammatory drugs, COX-2 and colorectal cancer. Toxicology Letters 112/113:493–498
    [Google Scholar]
  25. Peterhans E. 1997; Reactive oxygen species and nitric oxide in viral diseases. Biological Trace Element Research 56:107–116
    [Google Scholar]
  26. Primache V., Binda S., De Benedittis G., Barbi M. 1998; In vitro activity of acetylsalicylic acid on replication of varicella-zoster virus. New Microbiologica 21:397–401
    [Google Scholar]
  27. Raung S. L., Kuo M. D., Wang Y. M., Chen C. J. 2001; Role of reactive oxygen intermediates in Japanese encephalitis virus infection in murine neuroblastoma cells. Neuroscience Letters 315:9–12
    [Google Scholar]
  28. Ravi V., Parida S., Desai A., Chandramuki A., Gourie-Devi M., Grau G. E. 1997; Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients. Journal of Medical Virology 51:132–136
    [Google Scholar]
  29. Sagone A. L. Jr, Husney R. M. 1987; Oxidation of salicylates by stimulated granulocytes: evidence that these drugs act as free radical scavengers in biological systems. Journal of Immunology 138:2177–2183
    [Google Scholar]
  30. Schwarz K. B. 1996; Oxidative stress during viral infection: a review. Free Radical Biology and Medicine 21:641–649
    [Google Scholar]
  31. Schweizer M., Peterhans E. 1999; Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis. Journal of General Virology 80:1147–1155
    [Google Scholar]
  32. Schwenger P., Alpert D., Skolnik E. Y., Vilcek J. 1998; Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation. Molecular and Cellular Biology 18:78–84
    [Google Scholar]
  33. Segal R. A., Greenberg M. E. 1996; Intracellular signaling pathways activated by neurotrophic factors. Annual Review of Neuroscience 19:463–489
    [Google Scholar]
  34. Singh A., Kulshreshtha R., Mathur A. 2000; Secretion of the chemokine interleukin-8 during Japanese encephalitis virus infection. Journal of Medical Virology 49:607–612
    [Google Scholar]
  35. Speir E., Yu Z. X., Ferrans V. J., Huang E. S., Epstein S. E. 1998; Aspirin attenuates cytomegalovirus infectivity and gene expression mediated by cyclooxygenase-2 in coronary artery smooth muscle cells. Circulation Research 83:210–216
    [Google Scholar]
  36. Srivastava S., Khanna N., Saxena S. K., Singh A., Mathur A., Dhole T. N. 1999; Degradation of Japanese encephalitis virus by neutrophils. International Journal of Experimental Pathology 80:17–24
    [Google Scholar]
  37. Staal J. T., Roederer M., Herzenberg L. A., Herzenberg L. A. 1990; Intracellular thiols regulate activation of nuclear factor B and transcription of human immunodeficiency virus. Proceedings of the National Academy of Sciences, USA 87:9943–9947
    [Google Scholar]
  38. Stanciu M., Wang Y., Kentor R., Burke N., Watkins S., Kress G., Reynolds I., Klann E., Angiolieri M., Johnson J., Defranco D. B. 2000; Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. Journal of Biological Chemistry 275:12200–12206
    [Google Scholar]
  39. Vane J. R. 1971; Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 231:232–235
    [Google Scholar]
  40. Verhaegen S., McGowan A. J., Brophy A. R., Fernandes R. S., Cotter T. G. 1995; Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line. Biochemical Pharmacology 50:1021–1029
    [Google Scholar]
  41. Weissmann G. 1991; Aspirin. Scientific American 264:84–90
    [Google Scholar]
  42. Xia Z., Dickens M., Raingeaud J., Davis R. J., Greenberg M. E. 1995; Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331
    [Google Scholar]
  43. Zhu H., Bannenberg G. L., Moldeus P., Shertzer H. G. 1994; Oxidation pathways for the intracellular probe 2′,7′-dichlorofluorescein. Archives of Toxicology 68:582–587
    [Google Scholar]
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