Advertisement

European Archives of Oto-Rhino-Laryngology

, Volume 276, Issue 1, pp 131–137 | Cite as

The ratio of 11β-hydroxysteroid dehydrogenase 1/11β-hydroxysteroid dehydrogenase 2 predicts glucocorticoid response in nasal polyps

  • Lijie Jiang
  • Min Zhou
  • Jie Deng
  • Yueqi Sun
  • Kejun Zuo
  • Rui Zheng
  • Jianbo ShiEmail author
  • Yinyan LaiEmail author
Rhinology
  • 45 Downloads

Abstract

Background

Glucocorticoids are the first-line medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), whose local metabolism is catalyzed by 11β-HSD1 and 11β-HSD2. This study investigates the role of 11β-HSD1 and 11β-HSD2 on the glucocorticoid response of CRSwNP patients and the pathogenic mechanism of these polyps.

Methods

Forty-three adult CRSwNP patients were enrolled in this study. We evaluated the endoscopic scores by a nasal polyp grading system before and after treatment. We estimated the response to glucocorticoids by the total endoscopic scores. The logistic regression models and inflammatory characteristic curves were conducted to explore the prediction of the response to glucocorticoid in CRSwNP. The expression of 11β-HSD1 and 11β-HSD2 on human sinonasal epithelial cells (HSECS) was measured under the stimulation of toll-like receptor agonists and dexamethasone.

Results

The endoscopic scores in the CRSwNP group declined, the expression of 11β-HSD1/11β-HSD2 increased (r = 0.5276, P = 0.0011), and the cutoff value of the ratio of 11β-HSD1/11β-HSD2 was 0.4654 (sensitivity 79.17%, specificity 88.89%). Dexamethasone induced a decrease in the ratio of 11β-HSD1/11β-HSD2 (P = 0.049) by the stimulation of PGN-BS.

Conclusion

We found a strong correlation between the response to glucocorticoids and the ratio of 11β-HSD1/11β-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP. In addition, PGN-BS could also be a therapeutic target, as it is the negative factor that will decrease the sensitivity of glucocorticoids by reducing the ratio of 11β-HSD1/11β-HSD2.

Keywords

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) Glucocorticoid sensitivity Nasal polyps 

Abbreviations

11β-HSD1

11β-hydroxysteroid dehydrogenase 1

11β-HSD2

11β-hydroxysteroid dehydrogenase 2

NPA group

Nasal polyps with asthma group

NP-SR group

Nasal polyp sensitivity with glucocorticoids group

NP-CR group

Nasal polyp could not sensitivity with glucocorticoids group

Notes

Acknowledgements

We thank Prof. DeYun Wang for reviewing and revising the manuscript.

Funding

Natural Science Foundation of China, the Young Investigator Award, No. 81300814 for YYL. Natural Science Foundation of China, the General program project, No. 81470069 for JBS.

Compliance with ethical standards

Conflict of interest

The authors have declared that there is no conflict of interest.

Supplementary material

405_2018_5201_MOESM1_ESM.jpg (54 kb)
Supplementary material 1 (JPG 54 KB)
405_2018_5201_MOESM2_ESM.jpg (56 kb)
Supplementary material 2 (JPG 55 KB)
405_2018_5201_MOESM3_ESM.docx (15 kb)
Supplementary material 3 (DOCX 14 KB)

References

  1. 1.
    Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012(23):3 (preceding table of contents, 1–298) Google Scholar
  2. 2.
    Stevens WW, Schleimer RP, Kern RC (2016) Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract 4(4):565–572CrossRefGoogle Scholar
  3. 3.
    Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T et al (2012) Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy 67(1):91–98CrossRefGoogle Scholar
  4. 4.
    Bresciani M, Paradis L, Des Roches A, Vernhet H, Vachier I, Godard P et al (2001) Rhinosinusitis in severe asthma. J Allergy Clin Immunol 107(1):73–80CrossRefGoogle Scholar
  5. 5.
    Borish L (2015) Chronic rhinosinusitis: more than just “asthma of the upper airway”. Am J Respir Crit Care Med 192(6):647–648CrossRefGoogle Scholar
  6. 6.
    Stevens WW, Lee RJ, Schleimer RP, Cohen NA (2015) Chronic rhinosinusitis pathogenesis. J Allergy Clin Immunol 136(6):1442–1453CrossRefGoogle Scholar
  7. 7.
    Bose S, Grammer LC, Peters AT (2016) Infectious chronic rhinosinusitis. J Allergy Clin Immunol Pract 4(4):584–589CrossRefGoogle Scholar
  8. 8.
    Grzanka A, Misiolek M, Golusinski W, Jarzab J (2011) Molecular mechanisms of glucocorticoids action: implications for treatment of rhinosinusitis and nasal polyposis. Eur Arch Otorhinolaryngol 268(2):247–253CrossRefGoogle Scholar
  9. 9.
    Lee SH (2015) Mechanisms of glucocorticoid action in chronic rhinosinusitis. Allergy Asthma Immunol Res 7(6):534–537CrossRefGoogle Scholar
  10. 10.
    Orsida BE, Krozowski ZS, Walters EH (2002) Clinical relevance of airway 11 β-hydroxysteroid dehydrogenase type II enzyme in asthma. Am J Respir Crit Care Med 165(7):1010–1014CrossRefGoogle Scholar
  11. 11.
    Hennebold JD, Ryu SY, Mu HH, Galbraith A, Daynes RA (1996) 11 beta-hydroxysteroid dehydrogenase modulation of glucocorticoid activities in lymphoid organs. Am J Physiol 270(2):1296–1306Google Scholar
  12. 12.
    Chapman KE, Coutinho A, Gray M, Gilmour JS, Savill JS, Seckl JR (2006) Local amplification of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 and its role in the inflammatory response. Ann N Y Acad Sci 1088(1):265CrossRefGoogle Scholar
  13. 13.
    Chapman KE, Coutinho AE, Zhang Z, Kipari T, Savill JS, Seckl JR (2013) Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation. J Steroid Biochem Mol Biol 137(100):82CrossRefGoogle Scholar
  14. 14.
    Sai S, Esteves CL, Kelly V, Michailidou Z, Anderson K, Coll AP et al (2008) Glucocorticoid regulation of the promoter of 11beta-hydroxysteroid dehydrogenase type 1 is indirect and requires CCAAT/enhancer-binding protein-beta. Mol Endocrinol 22(9):2049–2060CrossRefGoogle Scholar
  15. 15.
    Ergang P, Leden P, Bryndova J, Zbankova S, Miksik I, Kment M et al (2008) Glucocorticoid availability in colonic inflammation of rat. Dig Dis Sci 53(8):2160–2167CrossRefGoogle Scholar
  16. 16.
    Abbott AN, Guidry TV, Welsh KJ, Thomas AM, Kling MA, Hunter RL et al (2009) 11beta-hydroxysteroid dehydrogenases are regulated during the pulmonary granulomatous response to the mycobacterial glycolipid trehalose-6,6′-dimycolate. Neuroimmunomodulation 16(3):147–154CrossRefGoogle Scholar
  17. 17.
    Stegk JP, Ebert B, Martin HJ, Maser E (2009) Expression profiles of human 11beta-hydroxysteroid dehydrogenases type 1 and type 2 in inflammatory bowel diseases. Mol Cell Endocrinol 301(1–2):104–108CrossRefGoogle Scholar
  18. 18.
    Jun YJ, Park SJ, Kim TH, Lee SH, Lee KJ, Hwang SM et al (2014) Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in patients with chronic rhinosinusitis and their possible contribution to local glucocorticoid activation in sinus mucosa. J Allergy Clin Immunol 134(4):926–934e6CrossRefGoogle Scholar
  19. 19.
    Reddel HK, Bateman ED, Becker A, Boulet LP, Cruz AA, Drazen JM et al (2015) A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J 46(3):622–639CrossRefGoogle Scholar
  20. 20.
    Meltzer EO, Hamilos DL, Hadley JA, Lanza DC, Marple BF, Nicklas RA et al (2006) Rhinosinusitis: developing guidance for clinical trials. J Allergy Clin Immunol 118(5 Suppl):S17–S61CrossRefGoogle Scholar
  21. 21.
    Milara J, Morell A, Ballester B, Armengot M, Morcillo E, Cortijo J (2017) MUC4 impairs the anti-inflammatory effects of corticosteroids in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 139(3):855–862e13CrossRefGoogle Scholar
  22. 22.
    Lai Y, Chen B, Shi J, Palmer JN, Kennedy DW, Cohen NA (2011) Inflammation-mediated upregulation of centrosomal protein 110, a negative modulator of ciliogenesis, in patients with chronic rhinosinusitis. J Allergy Clin Immunol 128(6):1207–1215e1CrossRefGoogle Scholar
  23. 23.
    Ma Y, Sun Y, Jiang L, Zuo K, Chen H, Guo J et al (2017) WDPCP regulates the ciliogenesis of human sinonasal epithelial cells in chronic rhinosinusitis. Cytoskeleton (Hoboken) 74(2):82–90CrossRefGoogle Scholar
  24. 24.
    Milara J, Peiro T, Armengot M, Frias S, Morell A, Serrano A et al (2015) Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 135(2):470–476CrossRefGoogle Scholar
  25. 25.
    Yang JY, Kim MS, Kim E, Cheon JH, Lee YS, Kim Y et al (2016) Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7-mediated interferon-beta production. Immunity 44(4):889–900CrossRefGoogle Scholar
  26. 26.
    Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature 413(6857):732–738CrossRefGoogle Scholar
  27. 27.
    Dziarski R, Gupta D (2005) Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect Immunity 73(8):5212CrossRefGoogle Scholar
  28. 28.
    Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA et al (2003) Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of toll-like receptor 7. Proc Natl Acad Sci USA 100(11):6646–6651CrossRefGoogle Scholar
  29. 29.
    Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S et al (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303(5663):1526–1529CrossRefGoogle Scholar
  30. 30.
    Funder JW (1997) Glucocorticoid and mineralocorticoid receptors: biology and clinical relevance. Annu Rev Med 48(1):231–240CrossRefGoogle Scholar
  31. 31.
    Suzuki S, Koyama K, Darnel A, Ishibashi H, Kobayashi S, Kubo H et al (2003) Dexamethasone upregulates 11beta-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells. Am J Respir Crit Care Med 167(9):1244–1249CrossRefGoogle Scholar
  32. 32.
    Park SJ, Kook JH, Kim HK, Kang SH, Lim SH, Kim HJ et al (2015) Macrolides increase the expression of 11beta-hydroxysteroid dehydrogenase 1 in human sinonasal epithelium, contributing to glucocorticoid activation in sinonasal mucosa. Br J Pharmacol 172(21):5083–5095CrossRefGoogle Scholar
  33. 33.
    Josephson MB, Jiao J, Xu S, Hu A, Paranjape C, Grunstein JS et al (2012) IL-13-induced changes in endogenous glucocorticoid metabolism in the lung regulate the proasthmatic response. Am J Physiol Lung Cell Mol Physiol 303(5):L382–L390CrossRefGoogle Scholar
  34. 34.
    Bryndova J, Zbankova S, Kment M, Pacha J (2004) Colitis up-regulates local glucocorticoid activation and down-regulates inactivation in colonic tissue. Scand J Gastroenterol 39(6):549–553CrossRefGoogle Scholar
  35. 35.
    Hardy R, Rabbitt EH, Filer A, Emery P, Hewison M, Stewart PM et al (2008) Local and systemic glucocorticoid metabolism in inflammatory arthritis. Ann Rheum Dis 67(9):1204–1210CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouPeople’s Republic of China

Personalised recommendations