Volume 97, Issue 1, Pages 90-96 (January 2003)

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ABSTRACT

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Expression of the glucocorticoid receptor alpha and beta isoforms in human nasal mucosa and polyp epithelial cells

Received 2 April 2002; accepted 12 June 2002.

Abstract

The lower sensitivity of the inflamed nasal mucosa to glucocorticoids might be related to an increased expression of the glucocorticoid receptor (GR) beta isoform. We investigated GR α and GR β mRNA expression in epithelial cells from nasal mucosa and nasal polyps. GR α mRNA was at least 1000 times more expressed than GR β mRNA in both tissues. GR β expression (mean±SEM of 103 cDNA copies/μg of total RNA) was higher in nasal polyps (1.15±0.19; n=27; P<0.01) than in nasal mucosa (0.62±0.10; n=32). Nasal polyps with>3% of inflammatory cells had higher GRβ levels (1.40±0.29; n=16) than both nasal mucosa (P<0.01) and polyps with ≤3% of inflammatory cells (0.80±0.18; n=11; P<0.05). No difference in GRβ expression was found between nasal mucosa and polyps with ≤ 3% of inflammatory cells. GR β expression correlated with the inflammatory cell number, especially with mast cells (r=0.50, P<0.0001). There was no difference in GR α mRNA expression between nasal mucosa and nasal polyps. In summary, GR α is far more expressed than GR β in both tissues. The increased expression of GR β may be related to the presence of inflammatory cells.

Keywords: glucocorticoid receptor isoforms, nasal mucosa, nasal polyp, epithelial cells, inflammatory cells.

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References

REFERENCES

1. 1 Mygind N, Dahl R, Larsen PL. Nasal polyposis. In: Szczeklik A, Gryglewski RJ, Vane JR editor. Eicosanoids, Aspirin, and Asthma. New York: Marcel Dekker, Inc; 1998;p. 473–491.

2. 2 Xaubet A, Mullol J, López E. Comparison of the role of nasal polyp and normal nasal mucosal epithelial cells on in vitro eosinophil survival. Mediation by GM-CSF and inhibition by dexamethasone. Clin Exp Allergy. 1994;24:307–317. MEDLINE | CrossRef

3. 3 Leung DY, de Castro M, Szefler SJ, Chrousos GP. Mechanisms of glucocorticoid-resistant asthma. Ann NY Acad Sci. 1998;840:735–746. MEDLINE | CrossRef

4. 4 Beato M, Truss M, Chávez S. Control of transcription by steroid hormones. Ann NY Acad Sci. 1996;784:93–123. MEDLINE | CrossRef

5. 5 Oakley RH, Sar M, Cidlowski JA. The human glucocorticoid receptor β isoform. Expression, biochemical properties, and putative function. J Biol Chem. 1996;271:9550–9559. MEDLINE | CrossRef

6. 6 Barnes J. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci. 1998;94:557–572.

7. 7 Hecht K, Carlstedt-Duke J, Stierna P, Gustafsson J-Å, Brönnegård M, Wikström A-C. Evidence that the β -isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. J Biol Chem. 1997;272:26 659–26 664.

8. 8 Oakley RH, Jewell CM, Yudt MR, Bofetiado DM, Cidlowski JA. The dominant negative activity of the human glucocorticoid receptor β isoform. Specificity and mechanisms of action. J Biol Chem. 1999;274:27 857–27 866.

9. 9 de Lange P, Koper JW, Brinkmann AO, de Jong FH, Lamberts S WJ. Natural variants of the β isoform of the human glucocorticoid receptor do not alter sensitivity to glucocorticoids. Mol Cell Endocrinol. 1999;153:163–168. MEDLINE | CrossRef

10. 10 Brogan IJ, Murray IA, Cerillo G, Needham M, White A, Davis J RE. Interaction of glucocorticoid receptor isoforms with transcription factors AP-1 and NF- κ B: lack of effect of glucocorticoid receptor β. Mol Cell Endocrinol. 1999;157:95–104. MEDLINE | CrossRef

11. 11 Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951–1958. MEDLINE | CrossRef

12. 12 Sher ER, Leung D YM, Surs W. Steroid-resistant asthma. Cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest. 1994;93:33–39. MEDLINE | CrossRef

13. 13 Leung D YM, Hamid Q, Vottero A. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor β. J Exp Med. 1997;186:1567–1574. MEDLINE | CrossRef

14. 14 Hamid QA, Wenzel SE, Hauk PJ. Increased glucocorticoid receptor β in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600–1604.

15. 15 Sousa AR, Lane SJ, Cidlowski JA, Staynov DZ, Lee TH. Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptorβ -isoform. J Allergy Clin Immunol. 2000;105:943–950. Abstract | Full Text | Full-Text PDF (295 KB) | CrossRef

16. 16 Honda M, Orii F, Ayabe T. Expression of glucocorticoid receptor β in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology. 2000;118:859–866. Abstract | Full Text | Full-Text PDF (132 KB) | CrossRef

17. 17 Hamilos DL, Leung D YM, Muro S. GR β expression in nasal polyps inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone. J Allergy Clin Immunol. 2001;108:59–68. Abstract | Full-Text PDF (218 KB) | CrossRef

18. 18 Shahidi H, Vottero A, Stratakis CA. Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia. Biochem Biophys Res Commun. 1999;254:559–565. CrossRef

19. 19 Okret S, Dong Y, Brönnegård M, Gustafsson J-Å. Regulation of glucocorticoid receptor expression. Biochimie. 1991;73:51–59. MEDLINE | CrossRef

20. 20 Pujols L, Mullol J, Pérez M. Expression of the human glucocorticoid receptor α and β isoforms in human respiratory epithelial cells and their regulation by dexamethasone. Am J Respir Cell Mol Biol. 2001;24:49–57. MEDLINE

21. 21 Knutsson PU, Brönnegård M, Marcus C, Stierna P. Regulation of glucocorticoid receptor mRNA in nasal mucosa by local administration of fluticasone and budesonide. J Allergy Clin Immunol. 1996;97:655–661. Abstract | Full Text | Full-Text PDF (1198 KB) | CrossRef

22. 22 Kawabori S, Denburg JA, Schwartz LB. Histochemical and immunohistochemical characteristics of mast cells in nasal polyps. Am J Respir Cell Mol Biol. 1992;6:37–43. MEDLINE

23. 23 Juan M, Mullol J, Roca-Ferrer J. Regulation of ICAM-3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone. Allergy. 1999;54:1293–1298.

24. 24 Siebert PD. Quantitative RT-PCR. Methods & Applications. Palo Alto: Clontech Laboratories, Inc; 1993;.

25. 25 Auboeuf D, Vidal H. The use of the reverse transcription-competitive polymerase chain reaction to investigate the in vivo regulation of gene expression in small tissue samples. Anal Biochem. 1997;245:141–148. MEDLINE | CrossRef

26. 26 Dahia P LM, Honegger J, Reincke M. Expression of glucocorticoid receptor gene isoforms in corticotropin-secreting tumors. J Clin Endocrinol Metab. 1997;82:1088–1093. CrossRef

27. 27 Gagliardo R, Chanez P, Vignola AM. Glucocorticoid receptor α and β in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7–13.

28. 28 Webster JC, Oakley RH, Jewell CM, Cidlowski JA. Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative β isoform: a mechanism for the generation of glucocorticoid resistance. PNAS. 2001;98:6865–6870. MEDLINE | CrossRef

29. 29 Oakley RH, Webster JC, Sar M, Parker CR, Cidlowski JA. Expression and subcellular distribution of the β -isoform of the human glucocorticoid receptor. Endocrinology. 1997;138:5028–5038. MEDLINE | CrossRef

30. 30 Christodoulopoulos P, Leung D YM, Elliott MW. Increased number of glucocorticoid receptor β -expressing cells in the airways in fatal asthma. J Allergy Clin Immunol. 2000;106:479–484. Abstract | Full Text | Full-Text PDF (119 KB) | CrossRef

31. 31 Strickland I, Kisich K, Hauk PJ. High constitutive glucocorticoid receptor beta in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids. J Exp Med. 2001;193:585–594. MEDLINE | CrossRef

32. 32 Hauk PJ, Hamid QA, Chrousos GP, Leung D YM. Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens. J Allergy Clin Immunol. 2000;105:782–787. Abstract | Full Text | Full-Text PDF (81 KB) | CrossRef

33. 33 Vottero A, Chrousos GP. Glucocorticoid receptor beta: view I. Trends Endocrinol Metab. 1999;10:333–338. CrossRef

34. 34 Carlstedt-Duke J. Glucocorticoid receptor β: view II. Trends Endocrinol Metab. 1999;10:339–342. CrossRef

a Institut d'Investigacions Biomèdiques August Pi i Sunyer

b Servei d'Otorinolaringologia

c Servei de Pneumologia i Al.lèrgia Respiratòria-Institut de Pneumologia i Cirurgia Toràcica, Hospital Clı́nic, Departament de Medicina, Universitat de Barcelona

d Servei d'Otorinolaringologia4, Hospital Municipal de Badalona, Catalonia, Spain

f1 Correspondence should be addressed to: Dr César Picado, MD, Servei de Pneumologia, Hospital Clı́nic, C/ Villarroel 170, 08036 Barcelona, Catalonia, Spain. Fax: +34 93 4515272; E-mail: cpicado@medicina.ub.es

PII: S0954-6111(02)91406-X

doi:10.1053/rmed.2002.1406

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