title: Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage.
abstract: Although 17beta-estradiol administration following trauma-hemorrhage attenuates plasma cytokines and alteration in immune cell cytokine production, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-alpha or ER-beta. Accordingly, we examined which ER subtype predominantly mediates the salutary effects of 17beta-estradiol on systemic inflammatory response/immune cell cytokine production in various tissues following trauma-hemorrhage. Male rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min) and fluid resuscitation. The ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), the ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), 17beta-estradiol (50 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation, and various measurements were made 24 h thereafter. 17beta-Estradiol or PPT administration following trauma-hemorrhage prevented the increase in plasma IL-6 and IL-10 levels that were observed in vehicle-treated animals. IL-6 and TNF-alpha production by Kupffer cells increased; however, splenic macrophages (SMPhi), alveolar macrophages (AMPhi), and peripheral blood mononuclear cells (PBMC) had decreased release of these cytokines after trauma-hemorrhage. IL-10 production, however, increased in all macrophage populations. Administration of 17beta-estradiol following trauma-hemorrhage prevented all of these alterations. PPT had the same effects as 17beta-estradiol on IL-6 and TNF-alpha production by Kupffer cells and SMPhi, and DPN had the same effects on AMPhi and PBMC. The same effects as 17beta-estradiol on IL-10 production were observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally effective on SMPhi and AMPhi. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17beta-estradiol on immune cell functions following trauma-hemorrhage.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 Univ. Blvd., Volker Hall, Rm. G094, Birmingham, AL 35294-0019, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D016207:Cytokines; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015850:Interleukin-6; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D016753:Interleukin-10; D004958:Estradiol