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

Academic Article


  • 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. © 2007 Wiley-Liss, Inc.
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    Author List

  • Suzuki T; Yu HP; Hsieh YC; Choudhry MA; Bland KI; Chaudry IH
  • Start Page

  • 662
  • End Page

  • 672
  • Volume

  • 214
  • Issue

  • 3