Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage.
Although 17beta-estradiol (E2) administration after trauma-hemorrhage (T-H) reduces tissue neutrophil sequestration in male rodents, it remains unknown which of the estrogen receptor (ER) subtypes mediates this effect and whether the same ER subtype is involved in all the tissues. We hypothesized that the salutary effects of E2 on attenuation of neutrophil accumulation following T-H are tissue and receptor subtype-specific. Male Sprague-Dawley rats underwent sham operation or T-H (mean blood pressure, 40 mmHg for 90 min and then resuscitation). E2 (50 microg/kg), ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropiolnitrile (DPN; 5 microg/kg), or vehicle (10% dimethyl sulfoxide) was administered subcutaneously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and intercellular adhesion molecule (ICAM)-1 levels in the liver, intestine, and lung were measured (n = 6 rats/group). ER-alpha and ER-beta mRNA levels in sham-operated rats were also determined. T-H increased MPO activity, CINC-1, CINC-3, and ICAM-1 levels in the liver, intestine, and lung. These parameters were improved significantly in rats receiving E2 after T-H. Administration of the ER-alpha agonist PPT but not the ER-beta agonist DPN improved the measured parameters in the liver. In contrast, DPN but not PPT significantly improved these parameters in the lung. In the intestine, ER subtype specificity was not observed. ER-alpha mRNA expression was highest in the liver, whereas ER-beta mRNA expression was greatest in the lung. Thus, the salutary effects of E2 administration on tissue neutrophil sequestration following T-H are receptor subtype and tissue-specific.
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Huang-Ping
HP
Yu
Tomoharu
T
Shimizu
Ya-Ching
YC
Hsieh
Takao
T
Suzuki
Mashkoor A
MA
Choudhry
Martin G
MG
Schwacha
Irshad H
IH
Chaudry
D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000819:agonists / Q000378:metabolism; D006470:Hemorrhage / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012039:Regional Blood Flow / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014781:Viscera / Q000098:blood supply / Q000276:immunology* / Q000503:physiopathology; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology / Q000503:physiopathology
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase