P M Hägg1, T Hurskainen, R Palatsi, M Ilves, A Oikarinen. 1. Department of Dermatology, University of Oulu and Clinical Research Center, Oulu University Hospital, PO Box 5000, Oulu, FIN 90014, Finland. paivi.hagg@oulu.fi
Abstract
BACKGROUND: Variable response to topical glucocorticoid therapy occurs in the treatment of severe atopic dermatitis (AD). Glucocorticoid receptor (GR)-beta does not bind glucocorticoids but antagonizes the activity of the classic GRalpha, and could thus account for glucocorticoid insensitivity. OBJECTIVES: To investigate GRalpha and GRbeta mRNA and protein expression in lymphocytes of patients with AD before and after treatment with topical corticosteroids. METHODS: Blood was collected from 11 healthy donors, 10 patients with mild AD and 13 patients with severe AD. mRNA was isolated from peripheral blood mononuclear cells. Expression of GRalpha and GRbeta mRNA was determined by reverse transcriptase-polymerase chain reaction and quantitated. Expression of the GRs was confirmed by Western blot analysis. RESULT: The expression of GRalpha mRNA was detected in all subjects. GRbeta mRNA was detected in four out of 11 healthy volunteers, five out of 10 patients with mild AD and 11 out of 13 patients with severe AD. The incidence of GRbeta mRNA expression was higher in patients with severe AD (85%) than in patients with mild AD (50%), and significantly higher than in healthy volunteers (36%, P = 0.033). Four of the 13 patients with severe AD showed a 3.3-13.2-fold increase in the expression of GRbeta mRNA during a 2-week treatment with topical corticosteroids. In these patients the response to topical corticosteroids was poor. CONCLUSIONS: Expression of GRbeta is increased during topical corticosteroid treatment in the lymphocytes of patients with AD and, in particular, glucocorticoid-insensitive AD is associated with increased expression of GRbeta.
BACKGROUND: Variable response to topical glucocorticoid therapy occurs in the treatment of severe atopic dermatitis (AD). Glucocorticoid receptor (GR)-beta does not bind glucocorticoids but antagonizes the activity of the classic GRalpha, and could thus account for glucocorticoid insensitivity. OBJECTIVES: To investigate GRalpha and GRbeta mRNA and protein expression in lymphocytes of patients with AD before and after treatment with topical corticosteroids. METHODS: Blood was collected from 11 healthy donors, 10 patients with mild AD and 13 patients with severe AD. mRNA was isolated from peripheral blood mononuclear cells. Expression of GRalpha and GRbeta mRNA was determined by reverse transcriptase-polymerase chain reaction and quantitated. Expression of the GRs was confirmed by Western blot analysis. RESULT: The expression of GRalpha mRNA was detected in all subjects. GRbeta mRNA was detected in four out of 11 healthy volunteers, five out of 10 patients with mild AD and 11 out of 13 patients with severe AD. The incidence of GRbeta mRNA expression was higher in patients with severe AD (85%) than in patients with mild AD (50%), and significantly higher than in healthy volunteers (36%, P = 0.033). Four of the 13 patients with severe AD showed a 3.3-13.2-fold increase in the expression of GRbeta mRNA during a 2-week treatment with topical corticosteroids. In these patients the response to topical corticosteroids was poor. CONCLUSIONS: Expression of GRbeta is increased during topical corticosteroid treatment in the lymphocytes of patients with AD and, in particular, glucocorticoid-insensitive AD is associated with increased expression of GRbeta.
Authors: Shinwu Jeong; Nitin Patel; Christopher K Edlund; Jaana Hartiala; Dennis J Hazelett; Tatsuo Itakura; Pei-Chang Wu; Robert L Avery; Janet L Davis; Harry W Flynn; Geeta Lalwani; Carmen A Puliafito; Hussein Wafapoor; Minako Hijikata; Naoto Keicho; Xiaoyi Gao; Pablo Argüeso; Hooman Allayee; Gerhard A Coetzee; Mathew T Pletcher; David V Conti; Stephen G Schwartz; Alexander M Eaton; M Elizabeth Fini Journal: Invest Ophthalmol Vis Sci Date: 2015-04 Impact factor: 4.799