Characterization of a Novel Oral Glucocorticoid System and Its Possible Role in Disease


Autoria(s): Cirillo, N.; Hassona, Y.; Pignatelli, M.; Gasparoto, T. H.; Morgan, D. J.; Prime, S. S.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

23/10/2013

23/10/2013

2012

Resumo

Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11 beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11 beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11 beta-HSD2 inhibitor 18 beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

School of Oral and Dental Science, University of Bristol

School of Oral and Dental Science, University of Bristol

Ministero dellIstruzione, dellUniversitae della Ricerca

Ministero dell'Istruzione, dell'Universita'e della Ricerca [MIUR-PRIN 2007]

CMM from the University of Bristol

CMM from the University of Bristol

Cancer Research UK

Cancer Research UK [C1484]

University of Jordan

University of Jordan

Identificador

JOURNAL OF DENTAL RESEARCH, THOUSAND OAKS, v. 91, n. 1, supl. 4, Part 1-2, pp. 97-103, JAN, 2012

0022-0345

http://www.producao.usp.br/handle/BDPI/35657

10.1177/0022034511427909

http://dx.doi.org/10.1177/0022034511427909

Idioma(s)

eng

Publicador

SAGE PUBLICATIONS INC

THOUSAND OAKS

Relação

JOURNAL OF DENTAL RESEARCH

Direitos

restrictedAccess

Copyright SAGE PUBLICATIONS INC

Palavras-Chave #ORAL MUCOSA #KERATINOCYTES #FIBROBLASTS #CORTISOL #PEMPHIGUS VULGARIS #ORAL CANCER #11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY #PEMPHIGUS-VULGARIS #HPA AXIS #SKIN #METHYLPREDNISOLONE #TYPE-1 #CANCER #KERATINOCYTES #REGULATOR #SURVIVAL #DENTISTRY, ORAL SURGERY & MEDICINE
Tipo

article

original article

publishedVersion