Gender difference in tumor necrosis factor-α production in human neutrophils stimulated by lipopolysaccharide and interferon-γ

Gender difference in tumor necrosis factor-α production in human neutrophils stimulated by lipopolysaccharide and interferon-γ
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DOI:
10.1016/j.bbrc.2013.10.042
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发表时间:
2013-11-08
影响因子:
3.1
通讯作者:
Kitagawa, Seiichi
Kitagawa, Seiichi
中科院分区:
生物学4区
文献类型:
--
作者:
Aomatsu, Megumi;Kato, Takayuki;Kitagawa, Seiichi

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通过使用年轻男性和女性的外周血中性粒细胞,探讨了脂多糖(LPS)和干扰素-γ(IFN-γ)刺激的人中性粒细胞产生肿瘤坏死因子-α(TNF-α)的性别差异。与雌性中性粒细胞相比,雄性中性粒细胞释放更多的 TNF-α,并且响应 LPS 刺激而表现出更强的丝裂原激活蛋白激酶和磷脂酰肌醇 3-激酶激活。通过用 IFN-γ 预处理细胞,LPS 诱导的 TNF-α 产生显着增强,并且雄性中性粒细胞中 IFN-γ 介导的启动显着大于雌性中性粒细胞。与雌性中性粒细胞相比,雄性中性粒细胞表现出更高的 TLR4 表达,但不表达 IFN-γ 受体,并且其表达通过 IFN-γ 或 IFN-γ 加 LPS 的刺激而增加。这些发现表明,男性中性粒细胞对 LPS 和 IFN-γ 刺激的反应性高于女性中性粒细胞,并表明中性粒细胞对 LPS 和 IFN-γ 反应性的性别差异是脓毒症结局的部分原因,其中绝经前女性与男性相比表现出良好的预后。 (C) 2013 Elsevier Inc. 保留所有权利。
The gender difference in tumor necrosis factor-alpha (TNF-alpha) production in human neutrophils stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was explored by using peripheral blood neutrophils from young men and women. As compared with female neutrophils, male neutrophils released greater amounts of TNF-alpha, and exhibited stronger activation of mitogen-activated protein kinases and phosphatidylinositol 3-kinase in response to LPS stimulation. LPS-induced TNF-alpha production was markedly enhanced by pretreatment of cells with IFN-gamma, and IFN-gamma-mediated priming in male neutrophils was significantly greater than that in female neutrophils. Male neutrophils showed higher expression of TLR4, but not IFN-gamma receptors, than female neutrophils, and its expression was increased by stimulation with IFN-gamma or IFN-gamma plus LPS. These findings indicate that male neutrophils show higher responsiveness to stimulation with LPS and IFN-gamma than female neutrophils, and suggest that the gender difference in neutrophil responsiveness to LPS and IFN-gamma is partly responsible for that in the outcome of sepsis, in which premenopausal women show a favorable prognosis as compared with men. (C) 2013 Elsevier Inc. All rights reserved.