DOI QR코드

DOI QR Code

Changes in 11β-Hydroxysteroid Dehydrogenase and Glucocorticoid Receptor Expression in Kawasaki Disease

  • Wang, Juanli (Department of Cardiology, Xi'an Children's Hospital) ;
  • Zhou, Nan (Department of Cardiology, Xi'an Children's Hospital) ;
  • Wu, Shouzhen (Department of Central Laboratory, Xi'an Children's Hospital) ;
  • Zhang, Xiaoyan (Department of Pediatric, Shanxi Povince Hospital) ;
  • Su, Decheng (Department of Central Laboratory, Xi'an Children's Hospital)
  • 투고 : 2016.07.18
  • 심사 : 2016.12.06
  • 발행 : 2017.05.31

초록

Background and Objectives: This study aims to investigate the significance of changes in the expression $11{\beta}$-hydroxysteroid dehydrogenase ($11{\beta}-HSD$) and glucocorticoid receptor (GR) for the development of Kawasaki disease (KD). Subjects and Methods: Real-time polymerase chain reaction was performed to determine the mRNA expression levels of GR and $11{\beta}-HSD$ in peripheral blood monocytes, both in the acute phase of the disease and after treatment. Western blotting was performed to determine the protein expression levels of GR and $11{\beta}-HSD$. Results:The expression levels of $GR{\beta}$, $GR{\beta}$, and $11{\beta}-HSD1$ mRNA in the acute phase were significantly higher than levels at baseline (p<0.01) and after treatment (p<0.05). The $11{\beta}-HSD2$ mRNA levels were lower in the acute phase than in the normal group (p<0.01), and they were significantly higher after treatment than before (p<0.01). Western blot results were consistent with the real-time PCR results. The coronary artery lesion group exhibited significantly different $11{\beta}-HSD2$ expression levels from that of the group with normal coronary arteries (p<0.01). Conclusion: GR and $11{\beta}-HSD$ expression changes in the acute phase of KD are important factors for regulating inflammatory responses in KD.

키워드

참고문헌

  1. Weng KP, Ou SF, Lin CC, Hsieh KS. Recent advances in the treatment of Kawasaki disease. J Chin Med Assoc 2011;74:481-4. https://doi.org/10.1016/j.jcma.2011.09.001
  2. Furukawa T, Kishiro M, Akimoto K, Nagata S, Shimizu T, Yamashiro Y. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child 2008;93:142-6. https://doi.org/10.1136/adc.2007.126144
  3. Kobayashi T, Kobayashi T, Arekawa H. Prednisolone therapy for Kawasaki disease. Nihon Rinsho 2014;72:1623-8.
  4. Jibiki T, Kato I, Shiohama T, et al. Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease. Pediatr Int 2011;53:729-35. https://doi.org/10.1111/j.1442-200X.2011.03338.x
  5. Shirley DA, Stephens I. Primary treatment of incomplete Kawasaki disease with infliximab and methylprednisolone in a patient with a contraindication to intravenous immune globulin. Pediatr Infect Dis J 2010;29:978-9. https://doi.org/10.1097/INF.0b013e3181e05564
  6. Lim YJ, Jung JW. Clinical outcomes of initial dexamethasone treatment combined with a single high dose of intravenous immunoglobulin for primary treatment of Kawasaki disease. Yonsei Med J 2014;55:1260-6. https://doi.org/10.3349/ymj.2014.55.5.1260
  7. Kobayashi T, Saji T, Otani T, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet 2012;379:1613-20. https://doi.org/10.1016/S0140-6736(11)61930-2
  8. Hadoke PW, Iqbal J, Walker BR. Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease. Br J Pharmacol 2009;156:689-712. https://doi.org/10.1111/j.1476-5381.2008.00047.x
  9. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011;335:2-13. https://doi.org/10.1016/j.mce.2010.04.005
  10. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005;47:232-4. https://doi.org/10.1111/j.1442-200x.2005.02033.x
  11. Subspecialty Group of Cardiology, the Society of Pediatrics, Chinese Medical Association. Clinical treatment recommendations of coronary artery lesions in Kawasaki disease. Chin J Pediatr 2012;50:746-9.
  12. Walker BR. Glucocorticoids and cardiovascular disease. Eur J Endocrinol 2007;157:545-59. https://doi.org/10.1530/EJE-07-0455
  13. Meduri GU, Tolley EA, Chrousos GP, Stentz F. Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammationinduced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 2002;165:983-91. https://doi.org/10.1164/ajrccm.165.7.2106014
  14. Kino T, Su YA, Chrousos GP. Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology. Cell Mol Life Sci 2009;66:3435-48. https://doi.org/10.1007/s00018-009-0098-z
  15. Garbrecht MR, Schmidt TJ, Krozowski ZS, Snyder JM. 11Betahydroxysteroid dehydrogenase type 2 and the regulation of surfactant protein A bydexamethasone metabolites. Am J Physiol Endocrinol Metab 2006;290:E653-60. https://doi.org/10.1152/ajpendo.00396.2005
  16. Holmes MC, Sangra M, French KL, et al. 11Beta-hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoid. Neuroscience 2006;137:865-73. https://doi.org/10.1016/j.neuroscience.2005.09.037
  17. Sano S, Nakagawa Y, Iwashima S, et al. Dynamics of endogenous glucocorticoid secretion and its metabolism in Kawasaki disease. Steroids 2010;75:848-52. https://doi.org/10.1016/j.steroids.2010.06.006
  18. Ignatova ID, Kostadinova RM, Goldring CE, Nawrocki AR, Frey FJ, Frey BM. Tumor necrosis factor-alpha upregulates 11beta-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding proteinbeta in HepG2 cells. Am J Physiol Endocrinol Metab 2009;296:E367-77. https://doi.org/10.1152/ajpendo.90531.2008
  19. Sai S, Esteves CL, Kelly V, et al. Glucocorticoid regulation of the promoter of 11beta-hydroxysteroid dehydrogenase type 1 is indirect and requires CCAAT/enhancer-binding protein-beta. Mol Endocrinol 2008;22:2049-60. https://doi.org/10.1210/me.2007-0489
  20. Chapman KE, Gilmour JS, Coutinho AE, Savill JS, Seckl JR. 11Betahydroxysteroid dehydrogenase type 1--a role in inflammation? Mol Cell Endocrinol 2006;248:3-8. https://doi.org/10.1016/j.mce.2005.11.036
  21. D'Attilio L, Diaz A, Santucci N, et al. Levels of inflammatory cytokines, adrenal steroids, and mRNA for $GR{\alpha}$, $GR{\beta}$ and $11{\beta}HSD1$ in TB pleurisy. Tuberculosis (Edinb) 2013;93:635-41. https://doi.org/10.1016/j.tube.2013.07.008
  22. Ogata S, Ogihara Y, Honda T, Kon S, Akiyama K, Ishii M. Corticosteroid pulse combination therapy for refractory Kawasaki disease: a randomized trial. Pediatrics 2012;129:e17-23. https://doi.org/10.1542/peds.2011-0148
  23. Chen S, Dong Y, Yin Y, Krucoff MW. Intravenous immunoglobulin plus corticosteroid to prevent coronary artery abnormalities in Kawasaki disease: a meta-analysis. Heart 2013;99:76-82. https://doi.org/10.1136/heartjnl-2012-302126

피인용 문헌

  1. The role of corticosteroids in the treatment of Kawasaki disease vol.18, pp.2, 2017, https://doi.org/10.1080/14787210.2020.1713752