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Altered Cyclooxygenase-2 Expression in Pulmonary Sarcoidosis is not Related to Clinical Classifications

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Abstract

Elevated COX-2 activity is associated with the development of chronic lung diseases leading to bronchial obstruction, including sarcoidosis. The aim of the study was to examine expression pattern of COX-2 messenger RNA (mRNA). Expression was performed by q-PCR method in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes in sarcoidosis patients (n = 61) and control group (n = 30). Analysis of COX-2 mRNA expression level in BAL fluid and PB revealed downregulation in sarcoidosis and control groups. In PB lymphocytes, the statistically significant difference between patients and controls was observed (P = 0.003, Mann–Whitney U test), with higher expression in patients. There were no statistically significant differences between patients without and with parenchymal involvement (stages I vs. II–IV), between patients with acute vs. insidious onset of disease and between patients with abnormal vs. normal spirometry (P > 0.05, Mann–Whitney U test). Results suggest that expression of COX-2 mRNA in patients with pulmonary sarcoidosis is not related to clinical classifications.

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References

  1. Iannuzzi, M.C., B.A. Rybicki, and A.S. Teirstein. 2007. Sarcoidosis. The New England Journal of Medicine 357: 2153–2165.

    Article  CAS  PubMed  Google Scholar 

  2. Baughman, R.P., A.S. Teirstein, M.A. Judson, M.D. Rossman, H. Yeager Jr., E.A. Bresnitz, L. DePalo, G. Hunninghake, M.C. Iannuzzi, C.J. Johns, et al. 2001. Clinical characteristics of patients in a case control study of sarcoidosis. American Journal of Respiratory and Critical Care Medicine 164: 1885–1889.

    Article  CAS  PubMed  Google Scholar 

  3. Pueringer, R.J., D.A. Schwartz, C.S. Dayton, S.R. Gilbert, and G.W. Hunninghake. 1993. The relationship between alveolar macrophage TNF, IL-1, and PGE2 release, alveolitis, and disease severity in sarcoidosis. Chest 3: 832–838.

    Article  Google Scholar 

  4. Coward, W.R., K. Watts, C.A. Feghali-Bostwick, A. Knox, and L. Pang. 2009. Defective histone acetylation is responsible for the diminished expression of cyclooxygenase 2 in idiopathic pulmonary fibrosis. Molecular and Cellular Biology 15: 4325–39.

    Article  Google Scholar 

  5. Bauman, K.A., S.H. Wettlaufer, K. Okunishi, K.M. Vannella, J.S. Stoolman, S.K. Huang, A.J. Courey, E.S. White, C.M. Hogaboam CM, R.H. Simon, et al. 2010. The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice. Journal of Clinical Investigation 6: 1950–60.

    Article  Google Scholar 

  6. Crofford, L.J. 1997. COX-1 and COX-2 tissue expression: Implications and predictions. Journal of Rheumatology. Supplement 49: 15–9.

    CAS  Google Scholar 

  7. Korn, J.H. 1983. Fibroblast prostaglandin E2 synthesis. Persistence of an abnormal phenotype after short-term exposure to mononuclear cell products. Journal of Clinical Investigation 5: 1240–1246.

    Article  Google Scholar 

  8. Goldstein, R.H., and P. Polgar. 1982. The effect and interaction of bradykinin and prostaglandins on protein and collagen production by lung fibroblasts. Journal of Biological Chemistry 15: 8630–8633.

    Google Scholar 

  9. Petkova, D.K., C.A. Clelland, J.E. Ronan, S. Lewis, and A.J. Knox. 2003. Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis. Histopathology 4: 381–386.

    Article  Google Scholar 

  10. O’Neill, G.P., and A.W. Ford-Hutchinson. 1993. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Letters 13: 156–160.

    Google Scholar 

  11. Asano, K., C.M. Lilly, and J.M. Drazen. 1996. Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured human lung epithelial cells. American Journal of Physiology 271: 126–131.

    Google Scholar 

  12. Xaubet, A., W.J. Fu, M. Li, A. Serrano-Mollar, J. Ancochea, M. Molina-Molina, E. Rodriguez-Becerra, F. Morell, J.M. Rodríguez-Arias, J. Pereda, et al. 2010. A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases 27: 121–130.

    CAS  PubMed  Google Scholar 

  13. Bonner, J.C., A.B. Rice, J.L. Ingram, C.R. Moomaw, A. Nyska, A. Bradbury, A.R. Sessoms, P.C. Chulada, D.L. Morgan, D.C. Zeldin, et al. 2002. Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis. American Journal of Pathology 161: 459–470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hodges, R.J., R.G. Jenkins, C.P. Wheeler-Jones, D.M. Copeman, S.E. Bottoms, G.J. Bellingan, C.B. Nanthakumar, G.J. Laurent, S.L. Hart, M.L. Foster, et al. 2004. Severity of lung injury in cyclooxygenase-2-deficient mice is dependent on reduced prostaglandin E(2) production. American Journal of Pathology 165: 1663–1676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lopez-Campos, J.L., D. Rodriguez-Rodriguez, E. Rodriguez-Becerra, I. Alfageme Michavila, J.F. Guerra, F.J. Hernandez, A. Casanova, J. de Córdoba Gamero Fernández, A. Romero-Ortiz, et al. 2009. Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis. Respiratory Medicine 103: 427–433.

    Article  PubMed  Google Scholar 

  16. Hill, M.R., A. Papafili, H. Booth, P. Lawson, M. Hubner, H. Beynon, C. Read, G. Lindahl, R.P. Marshall, R.J. McAnulty, et al. 2006. Functional prostaglandin-endoperoxide synthase 2 polymorphism predicts poor outcome in sarcoidosis. American Journal of Respiratory and Critical Care Medicine 15: 915–922.

    Article  Google Scholar 

  17. Ianuzzi, M.C., B.A. Rybicki, and A.S. Teirstein. 2007. Sarcoidosis. NEJM 357: 2153–2165.

    Article  Google Scholar 

  18. American Thoracic Society, European Respiratory Society, and World Association of Sarcoidosis and Other Granulomatous Disorders. 1999. Statement on sarcoidosis. American Journal Respiratory Critical Care Medicine 160: 736–755.

    Article  Google Scholar 

  19. Chciałowski, A., J. Chorostowska-Wynimko, A. Fal, R. Pawłowicz, and J. Domagał-Kulawik. 2011. Recommendation of the Polish Respiratory Society for bronchoalveolar lavage (BAL) sampling processing and analysis methods. Pneumonologia i Alergologia Polska 79: 75–89.

    PubMed  Google Scholar 

  20. Wilborn, J., L.J. Crofford, M.D. Burdick, S.L. Kunkel, R.M. Strieter, and M. Peters-Golden. 1995. Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2. Journal of Clinical Investigation 95: 1861–1868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Peebles, R.S.J., K. Hashimoto, J.D. Morrow, R. Dworski, R.D. Collins, Y. Hashimoto, J.W. Christman, K.H. Kang, K. Jarzecka, J. Furlong, et al. 2002. Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice. American Journal of Respiratory and Critical Care Medicine 165: 1154–1160.

    Article  PubMed  Google Scholar 

  22. Xaubet, A., J. Roca-Ferrer, L. Pujols, J. Ramírez, J. Mullol, A. Marin-Arguedas, A. Torrego, J.M. Gimferrer, and C. Picado. 2004. Cyclooxygenase-2 is up-regulated in lung parenchyma of chronic obstructive pulmonary disease and down-regulated in idiopathic pulmonary fibrosis. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases 21: 35–42.

    PubMed  Google Scholar 

  23. Lappi-Blanco, E., R. Kaarteenaho-Wiik, P.K. Maasilta, S. Anttila, P. Pääkkö, and H.J. Wolff. 2006. COX-2 is widely expressed in metaplastic epithelium in pulmonary fibrous disorders. American journal of Clinical Pathology 126: 717–24.

    Article  CAS  PubMed  Google Scholar 

  24. Christophi, G.P., T. Caza, C. Curtiss, D. Gumber, P.T. Massa, and S.K. Landas. 2014. Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis. Experimental and Molecular Pathology 96: 393–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hodges, R.J., R.G. Jenkins, C.P. Wheeler-Jones, D.M. Copeman, S.E. Bottoms, G.J. Bellingan, C.B. Nanthakumar, G.J. Laurent, S.L. Hart, and M.L. Foster. 2004. Severity of lung injury in cyclooxygenase-2-deficient mice is dependent on reduced prostaglandin E(2) production. American Journal of Pathology 165: 1663–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Brown, J.R., and R.N. DuBois. 2004. Cyclooxygenase as a target in lung cancer. Clinical Cancer Research 15: 4266–4269.

    Article  Google Scholar 

  27. Noor, A., and K.S. Knox. 2007. Immunopathogenesis of sarcoidosis. Clinics in Dermatology 25: 250–258.

    Article  PubMed  Google Scholar 

  28. Hastürk, S., B. Kemp, S.K. Kalapurakal, J.M. Kurie, W.K. Hong, and J.S. Lee. 2002. Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma. Cancer 15: 1023–1031.

    Article  Google Scholar 

  29. Zhou, T., W. Zhang, N.J. Sweiss, E.S. Chen, D.R. Moller, K.S. Knox, S.F. Ma, M.S. Wade, I. Noth, R.F. Machado, et al. 2012. Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis. PLoS ONE 7(9), e44818.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Davies, P., and D.E. MacIntyre: Prostaglandins and inflammation. Inflammation: Basic Principles and Clinical Correlates. J.I. Gallin, I.M.Goldstein, and R. Snyderman, editors. Raven Press, Ltd., New York. 123–137, 1992

  31. Pablos, J.L., B. Santiago, P.E. Carreira, M. Galindo, and J.J. Gomez-Reino. 1999. Cyclooxygenase-1 and -2 are expressed by human T cells. Clinical and Experimental Immunology 115: 86–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hinz, B., K. Brune, and A. Pahl. 2000. Prostaglandin E(2) upregulates cyclooxygenase-2 expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biochemical and Biophysical Research Communications 272: 744–748.

    Article  CAS  PubMed  Google Scholar 

  33. Bonazzi, A., M. Bolla, C. Buccellati, A. Hernandez, S. Zarini, T. Viganò, F. Fumagalli, S. Viappiani, S. Ravasi, P. Zannini, et al. 2000. Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. American Journal of Respiratory and Critical Care Medicine 162: 2272–2277.

    Article  CAS  PubMed  Google Scholar 

  34. Miyara, M., Z. Amoura, C. Parizot, C. Badoual, K. Dorgham, S. Trad, M. Kambouchner, D. Valeyre, C. Chapelon-Abric, P. Debré, et al. 2006. The immune paradox of sarcoidosis and regulatory T cells. Journal of Experimental Medicine 20: 359–370.

    Article  Google Scholar 

  35. Akasaki, Y., G. Liu, N.H. Chung, M. Ehtesham, K.L. Black, and J.S. Yu. 2004. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. Journal of Immunology 173: 4352–4359.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was financed by the Medical Univeristy of Lodz, number of subsidy: 503/1-151/-4/503-11-002.

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Correspondence to Ewa Brzeziańska-Lasota.

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The study was approved by the Ethics Committee at the Medical University of Lodz (RNN/141/10/KE). Written informed consent was obtained from each patient.

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The authors declare that they have no conflict of interest.

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Kiszałkiewicz, J., Piotrowski, W.J., Pastuszak-Lewandoska, D. et al. Altered Cyclooxygenase-2 Expression in Pulmonary Sarcoidosis is not Related to Clinical Classifications. Inflammation 39, 1302–1309 (2016). https://doi.org/10.1007/s10753-016-0362-y

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  • DOI: https://doi.org/10.1007/s10753-016-0362-y

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