Role of extracellular signal-regulated protein kinase (ERK) in 17beta-estradiol-mediated attenuation of lung injury after trauma-hemorrhage.

Abstract

BACKGROUND:

Extracellular signal-regulated protein kinase (ERK) is known to be involved in pro-inflammatory and chemotactic events in response to injury. The aim of this study is to elucidate whether ERK plays any role in 17beta-estradiol (E2)-mediated attenuation of lung injury and pro-inflammatory mediators after trauma-hemorrhage.

METHODS:

Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure approximately 40 mm Hg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle (cyclodextrin), E2 (1 mg/kg body weight [BW]), or the ERK inhibitor PD98059 (2 mg/kg BW). At 2 h after sham operation or trauma-hemorrhage, various parameters were measured.

RESULTS:

Trauma-hemorrhage led to a significant increase in lung ERK phosphorylation, which was associated with increased lung myeloperoxidase activity, wet-to-dry weight ratio, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1, and macrophage inflammatory protein-2 levels. Circulatory IL-6, TNF-alpha, and lactate levels were also increased after trauma-hemorrhage compared with shams. Administration of E2 or ERK inhibitor PD98059 after trauma-hemorrhage attenuated the trauma-hemorrhage-induced increase in lung injury markers, ERK phosphorylation and cytokines/chemokines, ICAM-1 production, as well as circulatory cytokines and lactate levels.

CONCLUSION:

These results collectively suggest that the salutary effects of E2 on the lung after trauma-hemorrhage are mediated via an ERK pathway and subsequent downregulation of pro-inflammatory mediator production.

• Authors: Jun-Te Hsu, Wen-Hong Kan, Chi-Hsun Hsieh, Mashkoor A Choudhry, Kirby I Bland, Irshad H Chaudry
• Journal: Surgery (Surgery) Vol. 145 Issue 2 Pg. 226-34 (Feb 2009) ISSN: 1532-7361 [Electronic] United States
• PMID: 19167979 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Chemokine CXCL1
• Chemokine CXCL2
• Cxcl1 protein, rat
• Estrogens
• Flavonoids
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Lactic Acid
• Estradiol
• Peroxidase
• Extracellular Signal-Regulated MAP Kinases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Acute Lung Injury (enzymology, etiology, prevention & control)
• Animals
• Biomarkers (metabolism)
• Chemokine CXCL1 (metabolism)
• Chemokine CXCL2 (metabolism)
• Down-Regulation
• Estradiol (therapeutic use)
• Estrogens (therapeutic use)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-6 (blood)
• Lactic Acid (blood)
• Liver (enzymology)
• Lung (enzymology, pathology)
• Male
• Peroxidase (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (complications, drug therapy, enzymology)
• Tumor Necrosis Factor-alpha (blood)