Are the protective effects of 17beta-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-alpha or ER-beta?
The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17beta-estradiol (E2) administration. However, it remains unknown which of the two estrogen-receptors, (ER)-alpha or ER-beta, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER-beta(-/-) transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and treated with E2 (50 microg/25 g) or ER-alpha agonist propyl pyrazole triol (PPT; 50 microg/25 g) following trauma-hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma-hemorrhage resulted in a significant increase in plasma tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma-hemorrhage produced a significant reduction in systemic TNF-alpha and IL-6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage.
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Frank
F
Hildebrand
William J
WJ
Hubbard
Mashkoor A
MA
Choudhry
Bjoern M
BM
Thobe
Hans-Christoph
HC
Pape
Irshad H
IH
Chaudry
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010052:Ovariectomy; D010636:Phenols; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013154:Spleen / Q000098:blood supply / Q000293:injuries* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology
D016207:Cytokines; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010636:Phenols; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D003208:Concanavalin A; D016753:Interleukin-10; D004958:Estradiol