1887

Abstract

Infection of cells with influenza A virus results in cell death with apoptotic characteristics. Apoptosis is regarded as a non-inflammatory process. However, during influenza an inflammatory response occurs in the airway epithelium. An examination of this apparent paradox was made using influenza A virus infection of human nasal and bronchiolar epithelial cells. Some cytokine genes (IL-18, CCL2 and CCL5) were expressed constitutively in nasal cells but no cytokine was released. In bronchiolar cells, IL-1, IL-6 and CXCL8 expression was constitutive, whilst CCL2 and CCL5 expression was upregulated following influenza virus infection. IL-6, CXCL8 and CCL5 were released but IL-1 and CCL2 were not. In bronchiolar cells, cell death was inhibited by the caspase-8 (Z-IETD-fmk) and pan-caspase (Z-VAD-fmk) inhibitors and these inhibitors enhanced expression of and increased the levels of the three secreted cytokines significantly. Thus, the amount of each cytokine released from bronchiolar cells is reduced during cell death, implying that the observed inflammatory response in influenza would be greater if cell death did not occur. Reduced cytokine release is also associated with fragmentation of the Golgi body, as the caspase inhibitors also rescued influenza A virus-induced fragmentation of the Golgi ribbon.

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2003-09-01
2021-03-08
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References

  1. Adachi M., Matsukura S., Tokunaga H., Kokubu F.. 1997; Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. Int Arch Allergy Immunol113:307–311
    [Google Scholar]
  2. Arndt U., Wennemuth G., Barth P., Nain M., Al-Abed Y., Meinhardt A., Gemsa D., Bacher M.. 2002; Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection. J Virol76:9298–9306
    [Google Scholar]
  3. Balachandran S., Kim C. N., Yeh W. C., Mak T. W., Bhalla K., Barber G. N.. 1998; Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling. EMBO J17:6888–6902
    [Google Scholar]
  4. Balachandran S., Roberts P. C., Kipperman T., Bhalla K. N., Compans R. W., Archer D. R., Barber G. N.. 2000; α / β interferons potentiate virus-induced apoptosis through activation of the FADD/Caspase-8 death signaling pathway. J Virol74:1513–1523
    [Google Scholar]
  5. Beck G. C., Yard B. A., Breedijk A. J., Van Ackern K., Van D., Woude F. J.. 1999; Release of CXC-chemokines by human lung microvascular endothelial cells (LMVEC) compared with macrovascular umbilical vein endothelial cells. Clin Exp Immunol118:298–303
    [Google Scholar]
  6. Bussfeld D., Kaufmann A., Meyer R. G., Gemsa D., Sprenger H.. 1998; Differential mononuclear leukocyte attracting chemokine production after stimulation with active and inactivated influenza A virus. Cell Immunol186:1–7
    [Google Scholar]
  7. Chen W. S., Calvo P. A., Malide D.. 10 other authors 2001; A novel influenza A virus mitochondrial protein that induces cell death. Nat Med7:1306–1312
    [Google Scholar]
  8. Choi A. M., Jacoby D. B.. 1992; Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. FEBS Lett309:327–329
    [Google Scholar]
  9. Chomczynski P., Sacchi N.. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162156–159
    [Google Scholar]
  10. Colamussi M. L., White M. R., Crouch E., Hartshorn K. L.. 1999; Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria. Blood93:2395–2403
    [Google Scholar]
  11. Collie M. H., Rushton D. I., Sweet C., Smith H.. 1980; Studies of influenza virus infection in newborn ferrets. J Med Microbiol13:561–571
    [Google Scholar]
  12. Danel C., Erzurum S. C., McElvaney N. G., Crystal R. G.. 1996; Quantitative assessment of the epithelial and inflammatory cell populations in large airways of normals and individuals with cystic fibrosis. Am J Respir Crit Care Med153:362–368
    [Google Scholar]
  13. Dodd D. A., Giddings T. H. Jr, Kirkegaard K.. 2002; Poliovirus 3A protein limits interleukin-6 (IL-6), IL-8, and β -interferon secretion during viral infection. J Virol75:8158–8165
    [Google Scholar]
  14. Doedens J. R., Giddings T. H., Kirkegaard K.. 1997; Inhibition of endoplasmic reticulum-to-Golgi traffic by poliovirus protein 3A: genetic and ultrastructural analysis. J Virol71:9054–9064
    [Google Scholar]
  15. Engelich G., White M., Hartshorn K. L.. 2001; Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae : role of respiratory burst. J Leukoc Biol69:50–56
    [Google Scholar]
  16. Fujimoto I., Takizawa T., Ohba Y., Nakanishi Y.. 1998; Co-expression of Fas and Fas-ligand on the surface of influenza virus-infected cells. Cell Death Differ5:426–431
    [Google Scholar]
  17. Hinshaw V. S., Olsen C. W., Dybdahl-Sissoko N., Evans D.. 1994; Apoptosis: a mechanism of cell killing by influenza A and B viruses. J Virol68:3667–3673
    [Google Scholar]
  18. Hofmann P., Sprenger H., Kaufmann A., Bender A., Hasse C., Nain M., Gemsa D.. 1997; Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response. J Leukoc Biol61:408–414
    [Google Scholar]
  19. Husseini R. H., Sweet C., Bird R. A., Collie M. H., Smith H.. 1983; Distribution of viral antigen in the lower respiratory tract of ferrets infected with a virulent influenza virus: production and release of virus from corresponding organ cultures. J Gen Virol64:589–598
    [Google Scholar]
  20. Ito T., Kobayashi Y., Morita T., Horimoto T., Kawaoka Y.. 2002; Virulent influenza A viruses induce apoptosis in chickens. Virus Res84:27–35
    [Google Scholar]
  21. Julkunen I., Melen K., Nyqvist M., Pirhonen J., Sareneva T., Matikainen S.. 2000; Inflammatory responses in influenza A virus infection. Vaccine19 (suppl. 1):S32–S37
    [Google Scholar]
  22. Julkunen I., Sareneva T., Pirhonen J., Ronni T., Melen K., Matikainen S.. 2001; Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev12:171–180
    [Google Scholar]
  23. Kaufmann A., Salentin R., Meyer R. G.. 7 other authors 2001; Defense against influenza A virus infection: essential role of the chemokine system. Immunobiology204:603–613
    [Google Scholar]
  24. Kujime K., Hashimoto S., Gon Y., Shimizu K., Horie T.. 2000; p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol164:3222–3228
    [Google Scholar]
  25. Lane J. D., Lucocq J., Pryde J., Barr F., Woodman P. G., Allan V. J., Lowe M.. 2002; Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. J Cell Biol156:495–509
    [Google Scholar]
  26. Lin C., Zimmer S. G., Lu Z., Holland R. E. J., Dong Q., Chambers T. M.. 2001; The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis. Virology287:202–213
    [Google Scholar]
  27. Lu Y., Wambach M., Katze M. G., Krug R. M.. 1995; Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology214:222–228
    [Google Scholar]
  28. Mancini M., Machamer C. E., Roy S., Nicholson D. W., Thornberry N. A., Casciola-Rosen L. A., Rosen A.. 2000; Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J Cell Biol149:603–612
    [Google Scholar]
  29. Matikainen S., Pirhonen J., Miettinen M., Lehtonen A., Govenius-Vintola C., Sareneva T., Julkunen I.. 2000; Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Virology276:138–147
    [Google Scholar]
  30. Matsukura S., Kokubu F., Noda H., Tokunaga H., Adachi M.. 1996; Expression of IL-6, IL-8 and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virus A. J Allergy Clin Immunol98:1080–1087
    [Google Scholar]
  31. Matsukura S., Kokubu F., Kubo H.. 8 other authors 1998; Expression of RANTES by normal airway epithelial cells after influenza virus A infection. Am J Respir Cell Mol Biol18:255–264
    [Google Scholar]
  32. Mohsin M. A., Morris S. J., Smith H., Sweet C.. 2002; Correlation between levels of apoptosis, levels of infection and haemagglutinin receptor binding interaction of various subtypes of influenza virus: does the viral neuraminidase have a role in these associations. Virus Res, 200285:123–131
    [Google Scholar]
  33. Mori I., Komatsu T., Takeuchi K., Nakakuki K., Sudo M., Kimura Y.. 1995; In vivo induction of apoptosis by influenza virus. J Gen Virol76:2869–2873
    [Google Scholar]
  34. Morris S. J., Price G. E., Barnett J. M., Hiscox S. A., Smith H., Sweet C.. 1999; Role of neuraminidase in influenza virus-induced apoptosis. J Gen Virol80:137–146
    [Google Scholar]
  35. Morris S. J., Smith H., Sweet C.. 2002; Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role. Arch Virol147:961–979
    [Google Scholar]
  36. Nain M., Hinder F., Gong J. H., Schmidt A., Bender A., Sprenger H., Gemsa D.. 1990; Tumor necrosis factor-α production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides. J Immunol145:1921–1928
    [Google Scholar]
  37. Nichols J. E., Niles J. A., Roberts N. J. Jr. 2001; Human lymphocyte apoptosis after exposure to influenza A virus. J Virol75:5921–5929
    [Google Scholar]
  38. Nilsen E. M., Johansen F. E., Jahnsen F. L., Lundin K. E., Scholz T., Brandtzaeg P., Haraldsen G.. 1998; Cytokine profiles of cultured microvascular endothelial cells from the human intestine. Gut42:635–642
    [Google Scholar]
  39. Pirhonen J., Sareneva T., Kurimoto M., Julkunen I., Matikainen S.. 1999; Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol162:7322–7329
    [Google Scholar]
  40. Pirhonen J., Sareneva T., Julkunen I., Matikainen S.. 2001; Virus infection induces proteolytic processing of IL-18 in human macrophages via caspase-1 and caspase-3 activation. Eur J Immunol31:726–733
    [Google Scholar]
  41. Price G. E., Fenton R. J., Smith H., Sweet C.. 1997; Are known pyrogenic cytokines responsible for fever in influenza?. J Med Virol52:336–340
    [Google Scholar]
  42. Raff M.. 1998; Cell suicide for beginners. Nature396:119–122
    [Google Scholar]
  43. Ronni T., Sareneva T., Pirhonen J., Julkunen I.. 1995; Activation of IFN- α , IFN- γ , MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells. J Immunol154:2764–2774
    [Google Scholar]
  44. Sansonetti P. J., Phalipon A., Arondel J., Thirumalai K., Banerjee S., Akira S., Takeda K., Zychlinsky A.. 2000; Caspase-1 activation of IL-1 β and IL-18 are essential for Shigella flexneri -induced inflammation. Immunity12:581–590
    [Google Scholar]
  45. Schultz-Cherry S., Hinshaw V. S.. 1996; Influenza virus neuraminidase activates latent transforming growth factor β . J Virol70:8624–8629
    [Google Scholar]
  46. Takizawa T., Matsukawa S., Higuchi Y., Nakamura S., Nakanishi Y., Fukuda R.. 1993; Induction of programmed cell death (apoptosis) by influenza virus infection in tissue culture cells. J Gen Virol74:2347–2355
    [Google Scholar]
  47. Takizawa T., Fukuda R., Miyawaki T., Ohashi K., Nakanishi Y.. 1995; Activation of the apoptotic Fas antigen-encoding gene upon influenza virus infection involving spontaneously produced β -interferon. Virology209:288–296
    [Google Scholar]
  48. Takizawa T., Tatematsu C., Ohashi K., Nakanishi Y.. 1999; Recruitment of apoptotic cysteine proteases (caspases) in influenza virus-induced cell death. Microbiol Immunol43:245–252
    [Google Scholar]
  49. Tan S. L., Katze M. G.. 1998; Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase. J Interferon Cytokine Res18:757–766
    [Google Scholar]
  50. Tan S. L., Katze M. G.. 1999; The emerging role of the interferon-induced PKR protein kinase as an apoptotic effector: a new face of death?. J Interferon Cytokine Res19:543–554
    [Google Scholar]
  51. Technau-Ihling K., Ihling C., Kromeier J., Brandner G.. 2001; Influenza A virus infection of mice induces nuclear accumulation of the tumor suppressor protein p53 in the lung. Arch Virol146:1655–1666
    [Google Scholar]
  52. Timofeeva T. A., Klenk H. D., Zhirnov O. P.. 2001; Identification of the protease-binding domain in the N-terminal region of influenza virus A matrix protein M1. Mol Biol35:411–416
    [Google Scholar]
  53. Tomita T., Jackson A. M., Hida N., Hayat M., Dixon M. F., Shimoyama T., Axon A. T., Robinson P. A., Crabtree J. E.. 2001; Expression of interleukin-18, a Th1 cytokine, in human gastric mucosa is increased in Helicobacter pylori infection. J Infect Dis183:620–627
    [Google Scholar]
  54. Toms G. L., Davies J. A., Woodward C. G., Sweet C., Smith H.. 1977; The relation of pyrexia and nasal inflammatory response to virus levels in nasal washings of ferrets infected with influenza viruses of differing virulence. Br J Exp Pathol58:444–458
    [Google Scholar]
  55. Zhirnov O. P., Konakova T. E., Wolff T., Klenk H. D.. 2002a; NS1 protein of influenza A virus down-regulates apoptosis. J Virol76:1617–1625
    [Google Scholar]
  56. Zhirnov O. P., Ksenofontov A. L., Kuzmina S. G., Klenk H. D.. 2002b; Interaction of influenza A virus M1 matrix protein with caspases. Biochemistry (Mosc.)67:534–539
    [Google Scholar]
  57. Zlotnik A., Yoshie O.. 2000; Chemokines: a new classification system and their role in immunity. Immunity12:121–127
    [Google Scholar]
  58. Zychlinsky A., Fitting C., Cavaillon J. M., Sansonetti P. J.. 1994; Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest94:1328–1332
    [Google Scholar]
  59. Zychlinsky A., Sansonetti P.. 1997a; Perspectives series: host/pathogen interactions. Apoptosis in bacterial pathogenesis.. J Clin Invest100:493–495
    [Google Scholar]
  60. Zychlinsky A., Sansonetti P. J.. 1997b; Apoptosis as a proinflammatory event: what can we learn from bacteria-induced cell death?. Trends Microbiol5:201–204
    [Google Scholar]
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