1887

Abstract

infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodelling. We investigated whether infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMCs) were cultured in the presence or absence of . Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor β, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in infected PBMCs. We conclude that infection may promote airway remodelling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.036624-0
2012-05-01
2024-10-09
Loading full text...

Full text loading...

/deliver/fulltext/jmm/61/5/705.html?itemId=/content/journal/jmm/10.1099/jmm.0.036624-0&mimeType=html&fmt=ahah

References

  1. Adcock I. M., Barnes P. J. 2008; Molecular mechanisms of corticosteroid resistance. Chest 134:394–401 [View Article][PubMed]
    [Google Scholar]
  2. Balin B. J., Little C. S., Hammond C. J., Appelt D. M., Whittum-Hudson J. A., Gérard H. C., Hudson A. P. 2008; Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease. J Alzheimers Dis 13:371–380[PubMed]
    [Google Scholar]
  3. Beatty W. L., Morrison R. P., Byrne G. I. 1994; Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 58:686–699[PubMed]
    [Google Scholar]
  4. Black P. N., Scicchitano R., Jenkins C. R., Blasi F., Allegra L., Wlodarczyk J., Cooper B. C. 2000; Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma. Eur Respir J 15:254–259 [View Article][PubMed]
    [Google Scholar]
  5. Bossé M., Chakir J., Rouabhia M., Boulet L. P., Audette M., Laviolette M. 1999; Serum matrix metalloproteinase-9 : tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma. Am J Respir Crit Care Med 159:596–602[PubMed] [CrossRef]
    [Google Scholar]
  6. Boulay M. E., Prince P., Deschesnes F., Chakir J., Boulet L. P. 2004; Metalloproteinase-9 in induced sputum correlates with the severity of the late allergen-induced asthmatic response. Respiration 71:216–224 [View Article][PubMed]
    [Google Scholar]
  7. Chen C. Z., Yang B. C., Lin T. M., Lee C. H., Hsiue T. R. 2009; Chronic and repeated Chlamydophila pneumoniae lung infection can result in increasing IL-4 gene expression and thickness of airway subepithelial basement membrane in mice. J Formos Med Assoc 108:45–52 [View Article][PubMed]
    [Google Scholar]
  8. Cho Y. S., Kim T. B., Lee T. H., Moon K. A., Lee J., Kim Y. K., Lee K. Y., Moon H. B. 2005; Chlamydia pneumoniae infection enhances cellular proliferation and reduces steroid responsiveness of human peripheral blood mononuclear cells via a tumor necrosis factor-α-dependent pathway. Clin Exp Allergy 35:1625–1631 [View Article][PubMed]
    [Google Scholar]
  9. Cook P. J., Davies P., Tunnicliffe W., Ayres J. G., Honeybourne D., Wise R. 1998; Chlamydia pneumoniae and asthma. Thorax 53:254–259 [View Article][PubMed]
    [Google Scholar]
  10. Fakhri S., Tulic M., Christodoulopoulos P., Fukakusa M., Frenkiel S., Leung D. Y. M., Hamid Q. A. 2004; Microbial superantigens induce glucocorticoid receptor β and steroid resistance in a nasal explant model. Laryngoscope 114:887–892 [View Article][PubMed]
    [Google Scholar]
  11. Goleva E., Li L. B., Eves P. T., Strand M. J., Martin R. J., Leung D. Y. M. 2006; Increased glucocorticoid receptor beta alters steroid response in glucocorticoid-insensitive asthma. Am J Respir Crit Care Med 173:607–616 [View Article][PubMed]
    [Google Scholar]
  12. Gueders M. M., Foidart J.-M., Noel A., Cataldo D. D. 2006; Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur J Pharmacol 533:133–144 [View Article][PubMed]
    [Google Scholar]
  13. Hahn D. L., Bukstein D., Luskin A., Zeitz H. 1998; Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma. Ann Allergy Asthma Immunol 80:45–49 [View Article][PubMed]
    [Google Scholar]
  14. Hamid Q. A., Wenzel S. E., Hauk P. J., Tsicopoulos A., Wallaert B., Lafitte J. J., Chrousos G. P., Szefler S. J., Leung D. Y. 1999; Increased glucocorticoid receptor beta in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med 159:1600–1604[PubMed] [CrossRef]
    [Google Scholar]
  15. Kaukoranta-Tolvanen S. S. E., Teppo A. M., Laitinen K., Saikku P., Linnavuori K., Leinonen M. 1996; Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response. Microb Pathog 21:215–221 [View Article][PubMed]
    [Google Scholar]
  16. Kelly E. A., Jarjour N. N. 2003; Role of matrix metalloproteinases in asthma. Curr Opin Pulm Med 9:28–33 [View Article][PubMed]
    [Google Scholar]
  17. Kim T. B., Moon K. A., Lee K. Y., Park C. S., Bae Y. J., Moon H. B., Cho Y. S. 2009; Chlamydophila pneumoniae triggers release of CCL20 and vascular endothelial growth factor from human bronchial epithelial cells through enhanced intracellular oxidative stress and MAPK activation. J Clin Immunol 29:629–636 [View Article][PubMed]
    [Google Scholar]
  18. 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 [View Article][PubMed]
    [Google Scholar]
  19. Leung D. Y., Hamid Q., Vottero A., Szefler S. J., Surs W., Minshall E., Chrousos G. P., Klemm D. J. 1997; Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med 186:1567–1574 [View Article][PubMed]
    [Google Scholar]
  20. Li P. L., Chen C. L., Bortell R., Campbell W. B. 1999; 11,12-Epoxyeicosatrienoic acid stimulates endogenous mono-ADP-ribosylation in bovine coronary arterial smooth muscle. Circ Res 85:349–356[PubMed] [CrossRef]
    [Google Scholar]
  21. Matsumoto H., Niimi A., Takemura M., Ueda T., Minakuchi M., Tabuena R., Chin K., Mio T., Ito Y. other authors 2005; Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma. Thorax 60:277–281 [View Article][PubMed]
    [Google Scholar]
  22. Mattos W., Lim S., Russell R., Jatakanon A., Chung K. F., Barnes P. J. 2002; Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest 122:1543–1552 [View Article][PubMed]
    [Google Scholar]
  23. Mautino G., Oliver N., Chanez P., Bousquet J., Capony F. 1997; Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics. Am J Respir Cell Mol Biol 17:583–591[PubMed] [CrossRef]
    [Google Scholar]
  24. Park C. S., Kim T. B., Moon K. A., Bae Y. J., Lee H. R., Jang M. K., Moon H. B., Cho Y. S. 2010; Chlamydophila pneumoniae enhances secretion of VEGF, TGF-beta and TIMP-1 from human bronchial epithelial cells under Th2 dominant microenvironment. Allergy Asthma Immunol Res 2:41–47 [View Article][PubMed]
    [Google Scholar]
  25. Pasternack R., Huhtala H., Karjalainen J. 2005; Chlamydophila (Chlamydia) pneumoniae serology and asthma in adults: a longitudinal analysis. J Allergy Clin Immunol 116:1123–1128 [View Article][PubMed]
    [Google Scholar]
  26. Patton D. L., Wølner-Hanssen P., Cosgrove S. J., Holmes K. K. 1990; The effects of Chlamydia trachomatis on the female reproductive tract of the Macaca nemestrina after a single tubal challenge following repeated cervical inoculations. Obstet Gynecol 76:643–650[PubMed]
    [Google Scholar]
  27. Pujols L., Mullol J., Torrego A., Picado C. 2004; Glucocorticoid receptors in human airways. Allergy 59:1042–1052 [View Article][PubMed]
    [Google Scholar]
  28. Pujols L., Mullol J., Picado C. 2007; Alpha and beta glucocorticoid receptors: relevance in airway diseases. Curr Allergy Asthma Rep 7:93–99 [View Article][PubMed]
    [Google Scholar]
  29. Rödel J., Prochnau D., Prager K., Pentcheva E., Hartmann M., Straube E. 2003; Increased production of matrix metalloproteinases 1 and 3 by smooth muscle cells upon infection with Chlamydia pneumoniae . FEMS Immunol Med Microbiol 38:159–164 [View Article][PubMed]
    [Google Scholar]
  30. Sousa A. R., Lane S. J., Cidlowski J. A., Staynov D. Z., Lee T. H. 2000; Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform. J Allergy Clin Immunol 105:943–950 [View Article][PubMed]
    [Google Scholar]
  31. Taniguchi Y., Iwasaki Y., Tsugita M., Nishiyama M., Taguchi T., Okazaki M., Nakayama S., Kambayashi M., Hashimoto K., Terada Y. 2010; Glucocorticoid receptor-β and receptor-γ exert dominant negative effect on gene repression but not on gene induction. Endocrinology 151:3204–3213 [View Article][PubMed]
    [Google Scholar]
  32. ten Brinke A. 2008; Risk factors associated with irreversible airflow limitation in asthma. Curr Opin Allergy Clin Immunol 8:63–69 [View Article][PubMed]
    [Google Scholar]
  33. von Hertzen L. C. 2002; Role of persistent infection in the control and severity of asthma: focus on Chlamydia pneumoniae . Eur Respir J 19:546–556 [View Article][PubMed]
    [Google Scholar]
  34. von Hertzen L. C., Vasankari T., Liippo K., Wahlström E., Puolakkainen M. 2002; Chlamydia pneumoniae and severity of asthma. Scand J Infect Dis 34:22–27 [View Article][PubMed]
    [Google Scholar]
  35. Watson C., Alp N. J. 2008; Role of Chlamydia pneumoniae in atherosclerosis. Clin Sci (Lond) 114:509–531 [View Article][PubMed]
    [Google Scholar]
  36. Wright H. R., Turner A., Taylor H. R. 2008; Trachoma. Lancet 371:1945–1954 [View Article][PubMed]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.036624-0
Loading
/content/journal/jmm/10.1099/jmm.0.036624-0
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
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