Salutary effects of 17β-estradiol on Peyer’s patch T cell functions following trauma–hemorrhage

Abstract

Although 17β-estradiol (E2) administration following trauma–hemorrhage (T–H) improves immune functions in male rodents, it remains unclear whether E2 has salutary effects on Peyer’s patch (PP) T cell functions. We hypothesized that T–H induces PP T cell dysfunction and E2 administration following T–H will improve PP T cell function. T–H was induced in male C3H/HeN mice (6–8 weeks) by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer’s lactate). Estrogen receptor (ER)-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), E2 (50 μg/kg), or vehicle was injected subcutaneously at resuscitation onset. Two hours later, mice were sacrificed and PP T cells isolated. PP T cell capacity to produce cytokines in response to in vitro stimulation, PP T cell proliferation and MAPK (p38, ERK-1/2, JNK) activation were measured. Results indicate PP T cell proliferation, cytokine production and MAPK activation decreased significantly following T–H. E2, PPT or DPN administration normalized these parameters. Since PPT or DPN administration following T–H was effective in normalizing PP T cell functions, the salutary effects of E2 are mediated via ER-α and ER-β.