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Molecular Medicine

, Volume 14, Issue 11–12, pp 689–696 | Cite as

Estradiol’s Salutary Effects on Keratinocytes Following Trauma-Hemorrhage Are Mediated by Estrogen Receptor (ER)-α and ER-β

  • Fariba Moeinpour
  • Mashkoor A. Choudhry
  • Luiz F. Poli de Figueiredo
  • Kirby I. Bland
  • Irshad H. Chaudry
Research Article

Abstract

Although administration of 17β-estradiol (estrogen) following trauma-hemorrhage attenuates the elevation of cytokine production and mitogen-activated protein kinase (MAPK) activation in epidermal keratinocytes, whether the salutary effects of estrogen are mediated by estrogen receptor (ER)-α or ER-β is not known. To determine which estrogen receptor is the mediator, we subjected C3H/HeN male mice to trauma-hemorrhage (2-cm midline laparotomy and bleeding of the animals to a mean blood pressure of 35 mmHg and maintaining that pressure for 90 min) followed by resuscitation with Ringer’s lactate (four times the shed blood volume). At the middle of resuscitation we subcutaneously injected ER-α agonist propyl pyrazole triol (PPT; 5 µg/kg), ER-β agonist diarylpropionitrile (DPN; 5 µg/kg), estrogen (50 µg/kg), or ER antagonist ICI 182,780 (150 µg/kg). Two hours after resuscitation, we isolated keratinocytes, stimulated them with lipopolysaccharide for 24 h (5 µg/mL for maximum cytokine production), and measured the production of interleukin (IL)-6, IL-10, IL-12, and TNF-α and the activation of MAPK. Keratinocyte cytokine production markedly increased and MAPK activation occurred following trauma-hemorrhage but were normalized by administration of estrogen, PPT, and DPN. PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-α and ER-β mediate the salutary effects of estrogen on keratinocytes after trauma-hemorrhage.

Notes

Acknowledgements

This work was supported by NIH grant R01 GM37127. The authors thank Dr. Takashi Kawasaki for his kind help with the trauma-hemorrhage procedure and Bobbi Smith for her assistance in manuscript preparation.

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Fariba Moeinpour
    • 1
  • Mashkoor A. Choudhry
    • 1
  • Luiz F. Poli de Figueiredo
    • 2
  • Kirby I. Bland
    • 1
  • Irshad H. Chaudry
    • 1
  1. 1.Center for Surgical Research and Department of SurgeryUniversity of Alabama at Birmingham, G094 Volker HallBirminghamUSA
  2. 2.Department of SurgeryUniversity of Sao Paulo School of MedicineSao PauloBrazil

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