Salutary effects of estrogen receptor-β agonist on lung injury after trauma-hemorrhage

Huang Ping Yu, Ya Ching Hsieh, Takao Suzuki, Tomoharu Shimizu, Mashkoor A. Choudhry, Martin G Schwacha, Irshad H. Chaudry

Research output: Contribution to journalArticle

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Abstract

Although 17β-estradiol (E2) administration after trauma-hemorrhage attenuates lung injury in male rodents, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β. We hypothesized that the salutary effects of E2 lung are mediated via ER-β. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). E2 (50 μg/kg), ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropiolnitrile (DPN; 5 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. At 24 h after trauma-hemorrhage or sham operation, bronchoalveolar fluid (BALF) was collected for protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels. Moreover, lung tissue was used for inducible nitric oxide synthase (iNOS) mRNA/protein expression, nitrate/nitrite and IL-6 levels, and wet/dry weight ratio (n = 6 rats/group). One-way ANOVA and Tukey's test were used for statistical analysis. The results indicated that E2 downregulated lung iNOS expression after trauma-hemorrhage. Protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels in BALF and nitrate/nitrite and IL-6 levels in the lung increased significantly after trauma-hemorrhage; however, administration of DPN but not PPT significantly improved all parameters. Moreover, DPN treatment attenuated trauma-hemorrhage- mediated increase in iNOS mRNA/protein expression in the lung. In contrast, no significant change in the above parameters was observed with PPT. Thus the salutary effects of E2 on attenuation of lung injury are mediated via ER-β, and ER-β-induced downregulation of iNOS likely plays a significant role in the DPN-mediated lung protection after trauma-hemorrhage.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Lung Injury
Estrogens
Hemorrhage
Estrogen Receptors
Nitric Oxide Synthase Type II
Nitrites
Wounds and Injuries
NAD
Nitrates
Lung
Interleukin-6
Resuscitation
Proteins
Down-Regulation
Messenger RNA
Dimethyl Sulfoxide
Sprague Dawley Rats
Estradiol
Rodentia
Analysis of Variance

Keywords

  • Diarylpropiolnitrile
  • Propyl pyrazole triol
  • Shock

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Salutary effects of estrogen receptor-β agonist on lung injury after trauma-hemorrhage. / Yu, Huang Ping; Hsieh, Ya Ching; Suzuki, Takao; Shimizu, Tomoharu; Choudhry, Mashkoor A.; Schwacha, Martin G; Chaudry, Irshad H.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 290, No. 5, 05.2006.

Research output: Contribution to journalArticle

Yu, Huang Ping ; Hsieh, Ya Ching ; Suzuki, Takao ; Shimizu, Tomoharu ; Choudhry, Mashkoor A. ; Schwacha, Martin G ; Chaudry, Irshad H. / Salutary effects of estrogen receptor-β agonist on lung injury after trauma-hemorrhage. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2006 ; Vol. 290, No. 5.
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abstract = "Although 17β-estradiol (E2) administration after trauma-hemorrhage attenuates lung injury in male rodents, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β. We hypothesized that the salutary effects of E2 lung are mediated via ER-β. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). E2 (50 μg/kg), ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropiolnitrile (DPN; 5 μg/kg), or vehicle (10{\%} DMSO) was injected subcutaneously during resuscitation. At 24 h after trauma-hemorrhage or sham operation, bronchoalveolar fluid (BALF) was collected for protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels. Moreover, lung tissue was used for inducible nitric oxide synthase (iNOS) mRNA/protein expression, nitrate/nitrite and IL-6 levels, and wet/dry weight ratio (n = 6 rats/group). One-way ANOVA and Tukey's test were used for statistical analysis. The results indicated that E2 downregulated lung iNOS expression after trauma-hemorrhage. Protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels in BALF and nitrate/nitrite and IL-6 levels in the lung increased significantly after trauma-hemorrhage; however, administration of DPN but not PPT significantly improved all parameters. Moreover, DPN treatment attenuated trauma-hemorrhage- mediated increase in iNOS mRNA/protein expression in the lung. In contrast, no significant change in the above parameters was observed with PPT. Thus the salutary effects of E2 on attenuation of lung injury are mediated via ER-β, and ER-β-induced downregulation of iNOS likely plays a significant role in the DPN-mediated lung protection after trauma-hemorrhage.",
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