Gender affects macrophage cytokine and prostaglandin E2 production and PGE2 receptor expression after trauma.
Gender affects macrophage cytokine and prostaglandin E2 production and PGE2 receptor expression after trauma.
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性别影响创伤后巨噬细胞细胞因子和前列腺素 E2 的产生以及 PGE2 受体的表达。
DOI：
10.1016/j.jss.2004.04.020
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Daly,JohnM
中科院分区：
文献类型：
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作者：
Stapleton,PhilipP;Strong,VivianEMack;Freeman,TracyA;Winter,Jordan;Yan,Zhaoping;Daly,JohnM
背景：性别影响损伤后的发病率和死亡率。荷尔蒙差异很重要；然而，前列腺素在创伤后与性别差异相关的免疫功能障碍中的中介作用尚不清楚。我们假设PGE2受体表达和信号的性别差异可能与免疫相关的差异有关。本研究测定了创伤后前列腺素受体亚型(EP1-EP4)的表达，并确定性别差异是否影响EP受体的表达。材料和方法：雄性和雌性小鼠(动情期和动情期前期)(每组6只)造成股骨骨折和40%的出血(创伤)或假损伤(麻醉)。7天后，取脾巨噬细胞，用脂多糖(O55：B5)刺激。结果发情前期雌性小鼠EP2-4受体的表达高于雄性小鼠。结果发情前期雌性小鼠EP2-4受体表达高于雄性小鼠。EP1受体的表达男性高于发情前期女性。雌性动情期小鼠创伤后四种受体的表达均较对照动情期小鼠减少。损伤雌性小鼠巨噬细胞PGE_2、肿瘤坏死因子-α和IL-6的产生显著高于雌性对照小鼠，而雄性小鼠与雄性对照小鼠相比无明显差异。创伤后雄性小鼠产生的前列腺素E_2和肿瘤坏死因子-α显著低于雌性创伤小鼠。结论创伤后雄性小鼠对创伤的反应存在性别差异，特定EP受体亚型的改变可能与创伤后免疫功能障碍有关。评估这些受体亚型的靶向调节的研究可能会为进一步了解损伤后免疫反应的性别差异提供进一步的见解。
BACKGROUNDGender influences morbidity and mortality after injury. Hormonal differences are important; however, the role of prostaglandins as mediators in immune dysfunction relating to gender differences after trauma is unclear. We hypothesized that gender-dependent differences in PGE2receptor expression and signaling may be involved in immune-related differences. This study determined prostaglandin receptor subtype (EP1–EP4) expression following injury and determined whether gender differences influence EP receptor expression.MATERIALS AND METHODSBALB/c male and female mice (estrus and pro-estrus) (n = 6 per group) were subjected to femur fracture and 40% hemorrhage (trauma) or sham injury (anesthesia). Seven days later, the splenic macrophages were harvested and stimulated with lipopolysaccharide (Escherichia coli serotype O55:B5). After 6 h mRNA samples were collected for EP receptor mRNA expression and at 24 h supernatants were collected for PGE2, TNF-α, and IL-6 production.RESULTSThe expression of EP2-4 receptors was higher in female pro-estrus mice compared with male mice. EP1 receptor expression was higher in males than pro-estrus females. There was decreased expression of all four receptors after trauma in female estrus compared with control estrus mice. Macrophage PGE2, TNF-α, and IL-6 production was significantly increased in injured female mice compared with female controls but there were no differences in injured male mice compared with male controls. PGE2and TNF-α production by traumatized male mice were significantly less than that produced by traumatized pro-estrus females.CONCLUSIONSThese data suggest gender-related differences in response to traumatic injury and that alterations in specific EP receptor subtypes may be involved in immune dysfunction after injury. Studies to evaluate targeted modulation of these receptor subtypes may provide further insights to gender-specific differences in the immune response after injury.