17beta-Estradiol's salutary effects on splenic dendritic cell functions following trauma-hemorrhage are mediated via estrogen receptor-alpha.
Although 17beta-estradiol administration following trauma-hemorrhage attenuates Kupffer cell, splenic and peritoneal macrophage functions, it remains unknown whether 17beta-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 17beta-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 approximately 90 min of hemorrhagic shock (blood pressure [BP] 35 mmHg), followed by fluid resuscitation (4x the shed blood volume in the form of Ringer's lactate). Estrogen receptor (ER)-alpha agonist propyl pyrazole triol (PPT; 5microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5microg/kg), 17beta-estradiol (50microg/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, 17beta-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, 17beta-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 17beta-estradiol on splenic DC functions are mediated predominantly via ER-alpha.
Kawasaki
Takashi
T
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Choudhry
Mashkoor A
MA
Suzuki
Takao
T
Schwacha
Martin G
MG
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008297:Male; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D010641:Phenotype; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000139:chemically induced / Q000378:metabolism*; D013154:Spleen / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D039521:CD11c Antigen; D016207:Cytokines; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D000949:Histocompatibility Antigens Class II; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol