1887

Journal of Medical Microbiology logo

Volume 52, Issue 5

Aspirin inhibits -induced NF-κB activation, cyclo-oxygenase-2 expression and prostaglandin E synthesis and attenuates chlamydial growth Free

Abstract

Infection with has been implicated as a potential risk factor for atherosclerosis. This study was designed to investigate the mechanisms of the anti-chlamydial activity of aspirin. A reporter gene assay for NF-κB activity, immunoblot analysis for cyclo-oxygenase (COX)-2 and radioimmunoassay for prostaglandin E (PGE) were performed. Following infection of HEp-2 cells with , NF-κB was activated, COX-2 was induced and PGE was elevated. Aspirin inhibited NF-κB activation at a concentration of 0.1 mM, partially inhibited COX-2 induction and blocked PGE synthesis completely. In addition, high doses of aspirin (1 and 2 mM) inhibited chlamydial growth in HEp-2 cells, decreasing the number and size of inclusion bodies; this effect could be overcome by adding tryptophan to the culture. Indomethacin also blocked the synthesis of PGE, but had no effect on COX-2 expression or chlamydial growth. These results indicate that aspirin not only has an anti-inflammatory activity through prevention of NF-κB activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.04992-0
2003-05-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jmm/52/5/JM520508.html?itemId=/content/journal/jmm/10.1099/jmm.0.04992-0&mimeType=html&fmt=ahah

References

  1. Appleby S. B, Ristimaki A, Neilson K, Narko K, Hla T. 1994; Structure of the human cyclo-oxygenase-2 gene. Biochem J 302:723–727
     [Google Scholar]
  2. Baeuerle P. A, Baltimore D. 1988; IκB: a specific inhibitor of the NF-κB transcription factor. Science 242:540–546 [CrossRef]
     [Google Scholar]
  3. Baeuerle P. A, Henkel T. 1994; Function and activation of NF-κB in the immune system. Annu Rev Immunol 12:141–179 [CrossRef]
     [Google Scholar]
  4. Brand K, Page S, Rogler G. 7 other authors 1996; Activated transcription factor nuclear factor-κB is present in the atherosclerotic lesion. J Clin Invest 97:1715–1722 [CrossRef]
     [Google Scholar]
  5. Budker V, Gurevich V, Hagstrom J. E, Bortzov F, Wolff J. A. 1996; pH-sensitive, cationic liposomes: a new synthetic virus-like vector. Nat Biotechnol 14:760–764 [CrossRef]
     [Google Scholar]
  6. Caldwell H. D, Kromhout J, Schachter J. 1981; Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis . Infect Immun 31:1161–1176
     [Google Scholar]
  7. Chu S. C, Marks-Konczalik J, Wu H. P, Banks T. C, Moss J. 1998; Analysis of the cytokine-stimulated human inducible nitric oxide synthase (iNOS) gene: characterization of differences between human and mouse iNOS promoters. Biochem Biophys Res Commun 248:871–878 [CrossRef]
     [Google Scholar]
  8. Collins T. 1993; Endothelial nuclear factor-κB and initiation of the atherosclerotic lesion. Lab Invest 68:499–508
     [Google Scholar]
  9. Cook P. J, Honeybourne D, Lip G. Y, Beevers D. G, Wise R, Davies P. 1998; Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia. Stroke 29:404–410 [CrossRef]
     [Google Scholar]
  10. Cybulsky M. I, Gimbrone M. A. Jr 1991; Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251:788–791 [CrossRef]
     [Google Scholar]
  11. D'Acquisto F, Iuvone T, Rombola L, Sautebin L, Di Rosa M, Carnuccio R. 1997; Involvement of NF-κB in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages. FEBS Lett 418:175–178 [CrossRef]
     [Google Scholar]
  12. Dechend R, Maass M, Gieffers J, Dietz R, Scheidereit C, Leutz A, Gulba D. C. 1999; Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF-κB and induces tissue factor and PAI-1 expression: a potential link to accelerated arteriosclerosis. Circulation 100:1369–1373 [CrossRef]
     [Google Scholar]
  13. Dichtl W, Nilsson L, Goncalves I, Ares M. P, Banfi C, Calara F, Hamsten A, Eriksson P, Nilsson J. 1999; Very low-density lipoprotein activates nuclear factor-κB in endothelial cells. Circ Res 84:1085–1094 [CrossRef]
     [Google Scholar]
  14. Gawaz M, Neumann F. J, Dickfeld T. 8 other authors 1998; Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 98:1164–1171 [CrossRef]
     [Google Scholar]
  15. Gierse J. K, Koboldt C. M, Walker M. C, Seibert K, Isakson P. C. 1999; Kinetic basis for selective inhibition of cyclo-oxygenases. Biochem J 339:607–614 [CrossRef]
     [Google Scholar]
  16. Goodwin J. S, Bankhurst A. D, Messner R. P. 1977; Suppression of human T-cell mitogenesis by prostaglandin.Existence of a prostaglandin-producing suppressor cell. J Exp Med 146:1719–1734 [CrossRef]
     [Google Scholar]
  17. Grayston J. T. 1992; Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis 15:757–761 [CrossRef]
     [Google Scholar]
  18. Grayston J. T, Kuo C. C, Wang S. P, Altman J. 1986; A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections. N Engl J Med 315:161–168 [CrossRef]
     [Google Scholar]
  19. Grayston J. T, Campbell L. A, Kuo C. C, Mordhorst C. H, Saikku P, Thom D. H, Wang S. P. 1990; A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 161:618–625 [CrossRef]
     [Google Scholar]
  20. Gupta S, Barrett T, Whitmarsh A. J, Cavanagh J, Sluss H. K, Derijard B, Davis R. J. 1996; Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15:2760–2770
     [Google Scholar]
  21. He X, Stuart J. M. 1999; Prostaglandin E2 selectively inhibits human CD4+ T cells secreting low amounts of both IL-2 and IL-4. J Immunol 163:6173–6179
     [Google Scholar]
  22. Jackson L. A, Campbell L. A, Kuo C. C, Rodriguez D. I, Lee A, Grayston J. T. 1997; Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 176:292–295 [CrossRef]
     [Google Scholar]
  23. Kol A, Bourcier T, Lichtman A. H, Libby P. 1999; Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Invest 103:571–577 [CrossRef]
     [Google Scholar]
  24. Kopp E, Ghosh S. 1994; Inhibition of NF-κB by sodium salicylate and aspirin. Science 265:956–959 [CrossRef]
     [Google Scholar]
  25. Krull M, Klucken A. C, Wuppermann F. N. 7 other authors 1999; Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae . J Immunol 162:4834–4841
     [Google Scholar]
  26. Kuo C. C, Shor A, Campbell L. A, Fukushi H, Patton D. L, Grayston J. T. 1993; Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis 167:841–849 [CrossRef]
     [Google Scholar]
  27. Marks-Konczalik J, Chu S. C, Moss J. 1998; Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor κB-binding sites. J Biol Chem 273:22201–22208 [CrossRef]
     [Google Scholar]
  28. Matsushima H, Shirai M, Ouchi K, Yamashita K, Kakutani T, Furukawa S, Nakazawa T. 1999; Lymphotoxin inhibits Chlamydia pneumoniae growth in HEp-2 cells. Infect Immun 67:3175–3179
     [Google Scholar]
  29. Melnick S. L, Shahar E, Folsom A. R, Grayston J. T, Sorlie P. D, Wang S. P, Szklo M. 1993; Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Am J Med 95:499–504 [CrossRef]
     [Google Scholar]
  30. Miyashita N, Toyota E, Sawayama T, Matsushima T. 1998; An association of an antibody against Chlamydia pneumoniae and coronary heart disease observed in Japan. Eur Heart J 19:971– 971 [CrossRef]
     [Google Scholar]
  31. Molestina R. E, Miller R. D, Lentsch A. B, Ramirez J. A, Summersgill J. T. 2000; Requirement for NF-κB in transcriptional activation of monocyte chemotactic protein 1 by Chlamydia pneumoniae in human endothelial cells. Infect Immun 68:4282–4288 [CrossRef]
     [Google Scholar]
  32. Neish A. S, Williams A. J, Palmer H. J, Whitley M. Z, Collins T. 1992; Functional analysis of the human vascular cell adhesion molecule 1 promoter. J Exp Med 176:1583–1593 [CrossRef]
     [Google Scholar]
  33. Ouchi K, Fujii B, Kanamoto Y, Karita M, Shirai M, Nakazawa T. 1998; Chlamydia pneumoniae in coronary and iliac arteries of Japanese patients with atherosclerotic cardiovascular diseases. J Med Microbiol 47:907–913 [CrossRef]
     [Google Scholar]
  34. Pantoja L. G, Miller R. D, Ramirez J. A, Molestina R. E, Summersgill J. T. 2000; Inhibition of Chlamydia pneumoniae replication in human aortic smooth muscle cells by gamma interferon-induced indoleamine 2,3-dioxygenase activity. Infect Immun 68:6478–6481 [CrossRef]
     [Google Scholar]
  35. Pantoja L. G, Miller R. D, Ramirez J. A, Molestina R. E, Summersgill J. T. 2001; Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon. Infect Immun 69:7927–7932 [CrossRef]
     [Google Scholar]
  36. Pistritto G, Franzese O, Pozzoli G, Mancuso C, Tringali G, Preziosi P, Navarra P. 1999; Bacterial lipopolysaccharide increases prostaglandin production by rat astrocytes via inducible cyclo-oxygenase: evidence for the involvement of nuclear factor κB. Biochem Biophys Res Commun 263:570–574 [CrossRef]
     [Google Scholar]
  37. Poston R. N, Haskard D. O, Coucher J. R, Gall N. P, Johnson-Tidey R. R. 1992; Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 140:665–673
     [Google Scholar]
  38. Ramirez J. A. 1996; Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. Ann Intern Med 125:979–982 [CrossRef]
     [Google Scholar]
  39. Ross R. 1993; The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809 [CrossRef]
     [Google Scholar]
  40. Saikku P, Leinonen M, Mattila K, Ekman M. R, Nieminen M. S, Makela P. H, Huttunen J. K, Valtonen V. 1988; Serological evidence of an association of a novel Chlamydia , TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet ii:983–986
     [Google Scholar]
  41. Shaper N. L, Hardiun-Lepers A, Shaper J. H. 1994; Male germ cell expression of murine β4-galactosyltransferase.A 796-base pair genomic region, containing two cAMP-responsive element (CRE)-like elements, mediates male germ cell-specific expression in transgenic mice. J Biol Chem 269:25165–25171
     [Google Scholar]
  42. Sharma S. A, Tummuru M. K. R, Blaser M. J, Kerr L. D. 1998; Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-κB in gastric epithelial cells. J Immunol 160:2401–2407
     [Google Scholar]
  43. Shirai M, Hirakawa H, Kimoto M. 8 other authors 2000; Comparison of whole genome sequences of Chlamydia pneumoniae J138 from Japan and CWL029 from USA. Nucleic Acids Res 28:2311–2314 [CrossRef]
     [Google Scholar]
  44. Shor A, Kuo C. C, Patton D. L. 1992; Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J 82:158–161
     [Google Scholar]
  45. Siebenlist U, Franzoso G, Brown K. 1994; Structure, regulation and function of NF-κB. Annu Rev Cell Biol 10:405–455 [CrossRef]
     [Google Scholar]
  46. Song Y. G, Kwon H. M, Kim J. M. 10 other authors 2000; Serologic and histopathologic study of Chlamydia pneumoniae infection in atherosclerosis: a possible pathogenetic mechanism of atherosclerosis induced by Chlamydia pneumoniae . Yonsei Med J 41:319–327 [CrossRef]
     [Google Scholar]
  47. 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. Circ Res 83:210–216 [CrossRef]
     [Google Scholar]
  48. Tiran A, Gruber H. J, Graier W. F, Wagner A. H, van Leeuwen E. B. M, Tiran B. 2002; Aspirin inhibits Chlamydia pneumoniae -induced nuclear factor-κB activation, cytokine expression, and bacterial development in human endothelial cells. Arterioscler Thromb Vasc Biol 22:1075–1080 [CrossRef]
     [Google Scholar]
  49. Traenckner E. B, Wilk S, Baeuerle P. A. 1994; A proteasome inhibitor prevents activation of NF-κB and stabilizes a newly phosphorylated form of IκB-α that is still bound to NF-κB. EMBO J 13:5433–5441
     [Google Scholar]
  50. Wimmer M. L. J, Sandmann-Strupp R, Saikku P, Haberl R. L. 1996; Association of chlamydial infection with cerebrovascular disease. Stroke 27:2207–2210 [CrossRef]
     [Google Scholar]
  51. Yamashita K, Ouchi K, Shirai M, Gondo T, Nakazawa T, Ito H. 1998; Distribution of Chlamydia pneumoniae infection in the atherosclerotic carotid artery. Stroke 29:773–778 [CrossRef]
     [Google Scholar]
  52. Yin M. J, Yamamoto Y, Gaynor R. B. 1998; The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β. Nature 396:77–80 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.04992-0
Loading
Aspirin inhibits Chlamydia pneumoniae-induced NF-κB activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth
J. Med. Microbiol. 52, 409 (2003); https://doi.org/10.1099/jmm.0.04992-0
/content/journal/jmm/10.1099/jmm.0.04992-0
/content/journal/jmm/10.1099/jmm.0.04992-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error