Document Detail

The role of estrogen receptor subtypes on hepatic neutrophil accumulation following trauma-hemorrhage: direct modulation of CINC-1 production by Kupffer cells.
MedLine Citation:
PMID:  18468914     Owner:  NLM     Status:  MEDLINE    
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.
Tomoharu Shimizu; Takao Suzuki; Huang-Ping Yu; Yukihiro Yokoyama; Mashkoor A Choudhry; Kirby I Bland; Irshad H Chaudry
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-05-12
Journal Detail:
Title:  Cytokine     Volume:  43     ISSN:  1096-0023     ISO Abbreviation:  Cytokine     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-24     Completed Date:  2008-08-12     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-92     Citation Subset:  IM    
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MeSH Terms
Cell Movement / drug effects,  physiology
Chemokine CXCL1 / biosynthesis*,  blood
Disease Models, Animal
Estrogen Receptor alpha / agonists,  physiology*
Estrogen Receptor beta / agonists,  physiology*
Hemorrhage / metabolism,  pathology*
Kupffer Cells / metabolism*,  physiology
Liver Diseases / metabolism*,  pathology*,  therapy
Neutrophil Infiltration / drug effects,  physiology*
Nitriles / administration & dosage
Propionates / administration & dosage
Pyrazoles / administration & dosage
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Chemokine CXCL1; 0/Cxcl1 protein, rat; 0/Estrogen Receptor alpha; 0/Estrogen Receptor beta; 0/Nitriles; 0/Propionates; 0/Pyrazoles; 0/diarylpropionitrile; 0/propyl pyrazole triol

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