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RECEPTORS AND SIGNAL TRANSDUCTION
-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
Submitted 15 September 2006 ; accepted in final form 4 February 2007
Although 17
-estradiol (E2) administration following trauma-hemorrhage prevents the suppression in splenocyte cytokine production, it remains unknown whether the salutary effects of 17
-estradiol are mediated via estrogen receptor (ER)-
or ER-
. Moreover, it is unknown which signaling pathways are involved in 17
-estradiol's salutary effects. Utilizing an ER-
- or ER-
-specific agonist, we examined the role of ER-
and ER-
in E2-mediated restoration of T-cell cytokine production following trauma-hemorrhage. Moreover, since MAPK, NF-
B, and activator protein (AP)-1 are known to regulate T-cell cytokine production, we also examined the activation of MAPK, NF-
B, and AP-1. Male rats underwent trauma-hemorrhage (mean arterial pressure 40 mmHg for 90 min) and fluid resuscitation. ER-
agonist propyl pyrazole triol (PPT; 5 µg/kg), ER-
agonist diarylpropionitrile (DPN; 5 µg/kg), 17
-estradiol (50 µg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic T cells were isolated, and their IL-2 and IFN-
production and MAPK, NF-
B, and AP-1 activation were measured. T-cell IL-2 and IFN-
production was decreased following trauma-hemorrhage, and this was accompanied with a decrease in T-cell MAPK, NF-
B, and AP-1 activation. PPT or 17
-estradiol administration following trauma-hemorrhage normalized those parameters, while DPN administration had no effect. Since PPT, but not DPN, administration following trauma-hemorrhage was as effective as 17
-estradiol in preventing the T-cell suppression, it appears that ER-
plays a predominant role in mediating the salutary effects of 17
-estradiol on T cells following trauma-hemorrhage, and that such effects are likely mediated via normalization of MAPK, NF-
B, and AP-1 signaling pathways.
shock; MAPK; NF-
B; activator protein-1; propyl pyrazole triol; diarylpropionitrile
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