The aim is to investigate that 17β-estradiol (E2)/
estrogen receptors (ERs) activation normalizes splenic CD4 + T lymphocytes proliferation and
cytokine production through inhibition of endoplasmic reticulum stress (ERS) following
hemorrhage. The results showed that
hemorrhagic shock (
hemorrhage through femoral artery, 38-42 mmHg for 90 min followed by
resuscitation of 30 min and subsequent observation period of 180 min) decreased the CD4+ T lymphocytes proliferation and
cytokine production after isolation and incubation with
Concanavalin A (5 μg/mL) for 48 h, induced the splenic injury with evidences of missed contours of the white pulp, irregular cellular structure, and typical inflammatory cell infiltration, upregulated the expressions of ERS
biomarkers 78 kDa
glucose-regulated
protein (
GRP78) and
activating transcription factor 6 (ATF6). Either E2, ER-α agonist
propyl pyrazole triol (PPT) or ERS inhibitor
4-Phenylbutyric acid administration normalized these parameters, while ER-β agonist
diarylpropionitrile administration had no effect. In contrast, administrations of either ERs antagonist
ICI 182,780 or G15 abolished the salutary effects of E2. Likewise, ERS inducer
tunicamycin induced an adverse effect similarly to that of
hemorrhagic shock in
sham rats, and aggravated
shock-induced effects, also abolished the beneficial effects of E2 and PPT, respectively. Together, the data suggest that E2 produces salutary effects on CD4+ T lymphocytes function, and these effects are mediated by ER-α and GPR30, but not ER-β, and associated with the attenuation of
hemorrhagic shock-induced ERS.