17 beta-estradiol administration following trauma-hemorrhage prevents the increase in Kupffer cell cytokine production and MAPK activation predominately via estrogen receptor-alpha.

Abstract

BACKGROUND:

17 beta-estradiol (E2) administration following trauma-hemorrhage (T-H) attenuates the elevation in plasma cytokines and Kupffer cell (KC) cytokine production; however, it remains unknown whether the salutary effects are mediated via estrogen receptor (ER)-alpha or ER-beta. We hypothesized that E2 mediates its salutary effects via ER-alpha and normalization of MAPK under those conditions.

METHODS:

Male rats underwent T-H (mean blood pressure [BP] 40 mmHg for 90 min) and fluid resuscitation. ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), E2 (50 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, KCs were isolated and their cytokine production (IL-6, TNF-alpha, IL-10) and MAPK activation were measured.

RESULTS:

Cytokine production increased after T-H, however, PPT or E2 administration after T-H normalized KC cytokine production. Although DPN attenuated increased production of these cytokines, KC capacity to produce the cytokines remained significantly higher than sham. PPT or E2 also prevented T-H-mediated activation of MAPK in KC. However, DPN did not prevent MAPK activation.

CONCLUSIONS:

Since PPT administration after T-H was more effective in decreasing KC cytokine production and MAPK activation than DPN, the salutary effects of E2 on KC functions are mediated predominantly via ER-alpha and normalization of MAPK following T-H.

• Authors: Takao Suzuki, Tomoharu Shimizu, Huang-Ping Yu, Ya-Ching Hsieh, Mashkoor A Choudhry, Kirby I Bland, Irshad H Chaudry
• Journal: Surgery (Surgery) Vol. 140 Issue 2 Pg. 141-8 (Aug 2006) ISSN: 0039-6060 [Print] United States
• PMID: 16904963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 2,3-bis(4-hydroxyphenyl)-propionitrile
• Cytokines
• Nitriles
• Phenols
• Propionates
• Pyrazoles
• Receptors, Estrogen
• 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
• Estradiol
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Cytokines (metabolism)
• Disease Models, Animal
• Estradiol (pharmacology)
• Hemorrhage (metabolism)
• Kupffer Cells (drug effects, metabolism)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• Nitriles (pharmacology)
• Phenols
• Propionates (pharmacology)
• Pyrazoles (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Estrogen (agonists, metabolism)
• Wounds, Penetrating (metabolism)