Estrogen receptor-alpha predominantly mediates the salutary effects of 17beta-estradiol on splenic macrophages following trauma-hemorrhage |
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Authors: | Suzuki Takao Shimizu Tomoharu Yu Huang-Ping Hsieh Ya-Ching Choudhry Mashkoor A Bland Kirby I Chaudry Irshad H |
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Institution: | Center for Surgical Research and Dept. of Surgery, Univ. of Alabama, at Birmingham, 1670 Univ. Blvd., Volker Hall, Rm. G094, Birmingham, AL 35294-0019, USA. |
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Abstract: | Although 17 -estradiol administration following trauma-hemorrhage prevents the suppression in splenic macrophage cytokine production, it remains unknown whether the salutary effects are mediated via estrogen receptor (ER)- or ER- and which signaling pathways are involved in such 17 -estradiol effects. Utilizing ER- - or ER- -specific agonists, this study examined the role of ER- and ER- in 17 -estradiol-mediated restoration of macrophage cytokine production following trauma-hemorrhage. In addition, since MAPK and NF- B are known to regulate macrophage cytokine production, we also examined the activation of those signaling molecules. Male rats underwent trauma-hemorrhage (mean arterial pressure of 40 mmHg for 90 min) and fluid resuscitation. The ER- agonist propyl pyrazole triol (PPT; 5 µg/kg), the ER- agonist diarylpropionitrile (DPN; 5 µg/kg), 17 -estradiol (50 µg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic macrophages were isolated, and their IL-6 and TNF- production and activation of MAPK and NF- B were measured. Macrophage IL-6 and TNF- production and MAPK activation were decreased, whereas NF- B activity was increased, following trauma-hemorrhage. PPT or 17 -estradiol administration after trauma-hemorrhage normalized those parameters. DPN administration, on the other hand, did not normalize the above parameters. Since PPT but not DPN administration following trauma-hemorrhage was as effective as 17 -estradiol in preventing the suppression in macrophage cytokine production, it appears that ER- plays the predominant role in mediating the salutary effects of 17 -estradiol on macrophage cytokine production following trauma-hemorrhage and that such effects are likely mediated via normalization of MAPK but not NF- B signaling pathways. shock; mitogen-activated protein kinase; nuclear factor- B; propyl pyrazole triol; diarylpropionitrile |
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