Stapleton Philip P, Strong Vivian E Mack, Freeman Tracy A, Winter Jordan, Yan Zhaoping, Daly John M
Weill Medical College of Cornell University, Department of Surgery, New York, New York, USA.
J Surg Res. 2004 Nov;122(1):1-7. doi: 10.1016/j.jss.2004.04.020.
Gender 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 PGE(2) receptor 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.
BALB/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 PGE(2), TNF-alpha, and IL-6 production.
The 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 PGE(2), TNF-alpha, 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. PGE(2) and TNF-alpha production by traumatized male mice were significantly less than that produced by traumatized pro-estrus females.
These 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.
性别影响损伤后的发病率和死亡率。激素差异很重要；然而，前列腺素作为创伤后与性别差异相关的免疫功能障碍介质的作用尚不清楚。我们假设前列腺素E2（PGE2）受体表达和信号传导中的性别依赖性差异可能与免疫相关差异有关。本研究确定了损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受体表达。
将BALB/c雄性和雌性小鼠（发情期和发情前期）（每组n = 6）进行股骨骨折和40%出血（创伤）或假损伤（麻醉）。7天后，收集脾巨噬细胞并用脂多糖（大肠杆菌血清型O55:B5）刺激。6小时后收集mRNA样本用于EP受体mRNA表达分析，24小时后收集上清液用于检测PGE2、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的产生。
与雄性小鼠相比，发情前期雌性小鼠中EP2-4受体的表达更高。雄性小鼠中EP1受体的表达高于发情前期雌性小鼠。与对照发情期小鼠相比，创伤后雌性发情期小鼠中所有四种受体的表达均降低。与雌性对照相比，受伤雌性小鼠巨噬细胞中PGE2、TNF-α和IL-6的产生显著增加，但与雄性对照相比，受伤雄性小鼠中无差异。创伤雄性小鼠产生的PGE2和TNF-α明显少于创伤发情前期雌性小鼠。
这些数据表明创伤性损伤反应存在性别相关差异，特定EP受体亚型的改变可能与损伤后免疫功能障碍有关。评估这些受体亚型靶向调节的研究可能为损伤后免疫反应中的性别特异性差异提供进一步的见解。
