TY - JOUR
T1 - Androgen and estrogen receptors in splenic T lymphocytes
T2 - Effects of flutamide and trauma-hemorrhage
AU - Samy, T. S.Anantha
AU - Schwacha, Martin G.
AU - Cioffi, William G.
AU - Bland, Kirby I.
AU - Chaudry, Irshad H.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000/10
Y1 - 2000/10
N2 - The endogenous sex steroids, testosterone and β-estradiol, play a major role in inflammatory processes. They regulate several cytokine genes by interaction with their intracellular receptors that are, essentially, transcription factors. Because T-lymphocyte functions are altered following trauma-hemorrhage in male mice, we investigated whether (i) receptors for androgen (AR) and estrogen (ER) are present in splenic T lymphocytes, (ii) receptor expressions are altered following trauma-hemorrhage, and (iii) pre-treatment of male mice with the AR antagonist, flutamide, alters receptor expressions and IL-6 release. Analysis of nuclear extracts indicated the presence of AR and ER in splenic T lymphocytes. No difference in receptor expressions between males and females or following trauma-hemorrhage was observed. Pre-treatment of males with flutamide, however, led to increased ER expression in T lymphocytes of sham and trauma-hemorrhaged animals. This suggested that flutamide is capable of inducing the expression of another receptor belonging to a different gonadal steroid. Because response elements for AR and ER are present in the promoter region of the IL-6 gene, release of IL-6 and expression of signal transducer and activator of transcription 3 (STAT3) were analyzed as functional parameters in splenic T lymphocytes. Trauma-hemorrhage decreased IL-6 release by T lymphocytes and the release was restored to sham levels with flutamide pre-treatment. Similarly, STAT3 expression was decreased in T lymphocytes following trauma-hemorrhage and the expression was restored by flutamide pre-treatment. These data collectively demonstrate the importance of gonadal steroids in the regulation of splenic T-lymphocyte functions.
AB - The endogenous sex steroids, testosterone and β-estradiol, play a major role in inflammatory processes. They regulate several cytokine genes by interaction with their intracellular receptors that are, essentially, transcription factors. Because T-lymphocyte functions are altered following trauma-hemorrhage in male mice, we investigated whether (i) receptors for androgen (AR) and estrogen (ER) are present in splenic T lymphocytes, (ii) receptor expressions are altered following trauma-hemorrhage, and (iii) pre-treatment of male mice with the AR antagonist, flutamide, alters receptor expressions and IL-6 release. Analysis of nuclear extracts indicated the presence of AR and ER in splenic T lymphocytes. No difference in receptor expressions between males and females or following trauma-hemorrhage was observed. Pre-treatment of males with flutamide, however, led to increased ER expression in T lymphocytes of sham and trauma-hemorrhaged animals. This suggested that flutamide is capable of inducing the expression of another receptor belonging to a different gonadal steroid. Because response elements for AR and ER are present in the promoter region of the IL-6 gene, release of IL-6 and expression of signal transducer and activator of transcription 3 (STAT3) were analyzed as functional parameters in splenic T lymphocytes. Trauma-hemorrhage decreased IL-6 release by T lymphocytes and the release was restored to sham levels with flutamide pre-treatment. Similarly, STAT3 expression was decreased in T lymphocytes following trauma-hemorrhage and the expression was restored by flutamide pre-treatment. These data collectively demonstrate the importance of gonadal steroids in the regulation of splenic T-lymphocyte functions.
KW - Androgen antagonist
KW - IL-6
KW - Immunosuppression
KW - STAT 3
KW - Sex steroid receptors
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U2 - 10.1097/00024382-200014040-00008
DO - 10.1097/00024382-200014040-00008
M3 - Article
C2 - 11049111
AN - SCOPUS:0034304562
VL - 14
SP - 465
EP - 470
JO - Shock
JF - Shock
SN - 1073-2322
IS - 4
ER -