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|Title:||Characterization of estrogen receptor mediating neutrophil function|
|Authors:||Noppawan Phumala Morales|
|Publisher:||The Thai Pharmacological and Therapeutic Society of Thailand.|
|Citation:||Thai J Pharmacol. 2010;32(1):276-280.|
|Abstract:||Estrogen and its receptors play important roles in the prevention of cardiovascular disease in women. 17β-estradiol (E2) has a direct role in the modulation of the innate immune function. 17β-E2 attenuates the production of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α. IL-8 production is also decreased by 17β-E2 in activated monocytes. Estrogen also has significant effects on neutrophil functions. Estrogen effects are mediated principally by two receptor subtypes, ERα and ERβ; both are expressed in endothelial, vascular smooth muscle cells, and immune cells. Both estrogen receptor subtypes are also expressed on human neutrophils, but their roles in mediating estrogen effects on neutrophil functions are remained to be elucidated. The purpose of this study was, therefore, to characterize the estrogen receptor subtypes that mediate estrogen effects on neutrophil functions. Neutrophils were isolated from post-menopausal women venous blood by Dextran and Percoll gradient centrifugation. All compounds were primarily investigated for their cytotoxic effects on neutrophils using XTT assay. Neutrophils were pre-incubated with 17β- E2, PPT (a selective ERα agonist), and DPN (a selective ERβ agonist), then activated by LPS or fMLP for the study of IL-8 production or adhesion molecule expression, respectively. The IL-8 production of leukocytes was assayed using ELISA. Neutrophil surface adhesion molecule expression was measured using flow cytometry. Neutrophil chemotaxis and superoxide anion generation (SAG) were also investigated. The results showed that 17β-E2 and PPT inhibited fMLP-induced CD62L-selectin shedding, while DPN did not. All drugs did not affect fMLP-induced MAC-1 expression. Both 17β-E2 and PPT attenuated IL-8 production in a dose-dependent manner. These results suggest the role of ERα on L-selectin shedding and IL-8 production in neutrophils. In addition, neutrophil chemotaxis-induced by rh IL-8 was inhibited by 17β-E2 and PPT, whereas SAG was inhibited by 17β-E2, PPT, and DPN. These results suggest that the inhibitory effect of 17β-E2 on neutrophil chemotaxis is mediated via ERα while both ERα and ERβ play roles in SAG.|
|Appears in Collections:||Pharmacology: National Journal Publications|
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