17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

Abstract

Although 17β-estradiol administration following trauma–hemorrhage attenuates Kupffer cell, splenic and peritoneal macrophage functions, it remains unknown whether 17β-estradiol has any salutary effects on splenic dendritic cell (DC) functions and if so, whether such effects are mediated via the estrogen receptors (ER). We hypothesized that 17β-estradiol administration following trauma–hemorrhage has salutary effects on splenic DC functions. Male C3H/HeN (6–8 weeks) mice were randomly assigned to sham operation or trauma–hemorrhage. Trauma–hemorrhage was induced by midline laparotomy and ∼90min of hemorrhagic shock (blood pressure [BP] 35mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer's lactate). Estrogen receptor (ER)-α agonist propyl pyrazole triol (PPT; 5μg/kg), ER-β agonist diarylpropionitrile (DPN; 5μg/kg), 17β-estradiol (50μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Two hours later, the mice were sacrificed, splenic DCs were isolated and the changes in their apoptosis, co-stimulating factors and MHC class II expression, ability to produce cytokines, and antigen presentation capacity were measured. Apoptosis of splenic DC increased following trauma–hemorrhage; however, 17β-estradiol administration after trauma–hemorrhage normalized the rate of apoptosis. Moreover, splenic DC cytokines production, co-stimulating factors and MHC class II expression, and antigen presentation capacity were significantly decreased following trauma–hemorrhage; however, 17β-estradiol as well as PPT also prevented these depressions. In contrast, DPN did not attenuate splenic DC functions following trauma–hemorrhage. Since PPT administration following trauma–hemorrhage was more effective in normalizing splenic DC functions than DPN, the salutary effects of 17β-estradiol on splenic DC functions are mediated predominantly via ER-α.