Estrogen-mediated activation of non-genomic pathway improves macrophages cytokine production following trauma-hemorrhage.
Although 17beta-estradiol (E2) attenuates the alterations in Kupffer cells and splenic macrophages (MPhi) cytokine production following trauma-hemorrhage, the mechanism by which this occurs remains unknown. Utilizing a cell-impermeable E2 conjugated with BSA (E2-BSA), we examined the non-genomic effects of E2 on the above two cell population cytokine production, MAPK and transcription factors activation following trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean BP 40 mmHg for 90 min, then resuscitation). E2, E2-BSA (1 mg/kg E2) with or without an estrogen receptor antagonist (ICI 182,780), or vehicle was administrated during resuscitation. Two hrs thereafter, Kupffer cells and SMPhi production of IL-6, TNF-alpha, and IL-10, activation of MAPK (p38, ERK-1/2, and JNK), and transcription factors (NF-kappaB and AP-1) were determined. IL-6, TNF-alpha, and IL-10 productive capacity, MAPK, and transcription factors activation increased in Kupffer cells while they decreased in SMPhi following trauma-hemorrhage. However, E2 administration normalized all of these alterations. Although E2-BSA also attenuated the alterations in cytokine production/transcription factors, the values were higher in Kupffer cells and lower in SMPhi compared to shams. In contrast, E2-BSA prevented trauma-hemorrhage-mediated changes in MAPK activation to the same extent as E2. Co-administration of ICI 182,780 abolished E2-BSA effects. Although some MAPK inhibitors suppressed cytokine production, the inhibitor effectiveness was dependent on cytokine, cell type and animal condition (trauma-hemorrhage or sham). Thus, E2 effects on Kupffer cells and SMPhi cytokine production and transcription factors activation following trauma-hemorrhage are mediated at least in part via non-genomic pathway and these non-genomic effects are likely mediated via MAPK pathways.
Suzuki
Takao
T
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Yu
Huang-Ping
HP
Hsieh
Ya-Ching
YC
Choudhry
Mashkoor A
MA
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016678:Genome; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism