title: The role of estrogen receptor subtypes on hepatic neutrophil accumulation following trauma-hemorrhage: direct modulation of CINC-1 production by Kupffer cells.
abstract: Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) reduces liver injury by decreasing neutrophil accumulation via estrogen receptor (ER)-alpha, it remains unclear whether cytokine-induced neutrophil chemoattractant (CINC)-1 production by Kupffer cells (KC) is directly modulated by ER-alpha under such condition. Male rats underwent laparotomy and hemorrhagic shock (40 mmHg for 90 min), followed by resuscitation with four times the shed blood volume in the form of Ringer's lactate. ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), E2 (50 microg/kg), or vehicle (10% DMSO) was administered subcutaneously during resuscitation; rats were sacrificed 24h thereafter. KC were isolated and cultured with ER agonists to examine if they directly affect CINC-1 production. T-H increased plasma alanine aminotransferase (ALT; hepatic injury) and hepatic myeloperoxidase (MPO) activity. E2, PPT and DPN administration reduced increased ALT; however, PPT was more effective than DPN. PPT and E2, but not DPN significantly attenuated increased hepatic MPO activity and CINC-1 levels. PPT addition in vitro (10(-7) and 10(-6)M) significantly reduced KC CINC-1 production. In summary, the salutary effects of E2 against hepatic injury are mediated predominantly via ER-alpha which directly modulates KC CINC-1 production and hepatic neutrophil accumulation following T-H.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, G094 Volker Hall, 1670 University Boulevard, Birmingham, AL 35294-0019, USA.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D054360:Chemokine CXCL1 / Q000096:biosynthesis* / Q000097:blood; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000502:physiology*; D005260:Female; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism* / Q000502:physiology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000008:administration & dosage; D010636:Phenols; D011422:Propionates / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol