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Published online before print June 22, 2007

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(Journal of Leukocyte Biology. 2007;82:774-780.)
© 2007 by Society for Leukocyte Biology

Mechanism of the nongenomic effects of estrogen on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of the PI-3K/Akt pathway

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA

² Correspondence: Center for Surgical Research, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL 35294-0019, USA. E-mail: irshad.chaudry{at}ccc.uab.edu

As studies indicate that genomic and nongenomic pathways are involved in mediating the salutary effects of 17ß-estradiol (E2) following trauma-hemorrhage, we examined if the nongenomic effects of E2 on attenuation of intestinal injury after trauma-hemorrhage involve the PI-3K/Akt pathway. Male Sprague-Dawley rats (300 g body weight) underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min), followed by resuscitation. E2 conjugated to BSA (E2-BSA; 1 mg/Kg E2), with or without an estrogen receptor antagonist (ICI 182,780), a PI-3K inhibitor (Wortmannin), or vehicle, was injected i.v. during resuscitation. At 2 h after trauma-hemorrhage or sham operation, intestinal myeloperoxidase (MPO) activity, ICAM-1, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and IL-6 levels were measured (n=6 rats/group). Intestinal PI-3K, phosphorylation of Akt (p-Akt), and Akt protein expressions were also determined. One-way ANOVA and Tukey’s test were used for statistical analysis. The results indicated that trauma-hemorrhage increased intestinal MPO activity and ICAM-1, CINC-1, CINC-3, and IL-6 levels. These parameters were improved significantly in the E2- or E2-BSA-treated rats subjected to trauma-hemorrhage. Although trauma-hemorrhage decreased intestinal PI-3K and p-Akt protein expressions, E2 or E2-BSA treatment following trauma-hemorrhage prevented such decreases in intestinal PI-3K and p-Akt protein expressions. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of E2-BSA on attenuation of intestinal injury following trauma-hemorrhage. Thus, the PI-3K/Akt pathway plays a critical role in mediating the nongenomic, salutary effects of E2 on attenuation of shock-induced intestinal tissue damage.

Key Words: shock • hormones • receptors • ICAM-1 • CINC-1 • CINC-3

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