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Estrogen-mediated activation of non-genomic pathway improves macrophages cytokine production following trauma-hemorrhage

Authors

  • Takao Suzuki,

    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
    Current affiliation:
    1. Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
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  • Huang-Ping Yu,

    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
    Current affiliation:
    1. Department of Anesthesiology, College of Medicine Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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  • Ya-Ching Hsieh,

    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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  • Mashkoor A. Choudhry,

    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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  • Kirby I. Bland,

    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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  • Irshad H. Chaudry

    Corresponding author
    1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
    • Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL 35294-0019.
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Abstract

Although 17β-estradiol (E2) attenuates the alterations in Kupffer cells and splenic macrophages (MΦ) 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 SMΦ production of IL-6, TNF-α, and IL-10, activation of MAPK (p38, ERK-1/2, and JNK), and transcription factors (NF-κB and AP-1) were determined. IL-6, TNF-α, and IL-10 productive capacity, MAPK, and transcription factors activation increased in Kupffer cells while they decreased in SMΦ 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 SMΦ 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 SMΦ 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. J. Cell. Physiol. 214: 662–672, 2008. © 2007 Wiley-Liss, Inc.

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