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首页> 外文期刊>International Journal of Burns and Trauma >Burn injury induces high levels of phosphorylated insulin-like growth factor binding protein-1
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Burn injury induces high levels of phosphorylated insulin-like growth factor binding protein-1

机译：烧伤导致高水平的磷酸化胰岛素样生长因子结合蛋白-1

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Purpose: Burn injury is associated with early apoptotic death of T cells. Insulin-like growth factor-1 (IGF-I) is able to protect T cells from apoptosis. Association of IGF-I with its IGFBP (Binding Protein)-1 limits its bioavailability and serine phosphorylation of IGFBP-1 lowers this further because of an increased affinity for IGF-I. The level of phosphorylated IGFBP-1 has been shown to increase in pediatric burn patients. Thus we hypothesized that a longitudinal study of burn patients would demonstrate 1) increased IGFBP-1 levels, 2) increased IGFBP-1 phosphorylation and 3) decreased IGF-I levels over time. Methods: We conducted a prospective observational study in adult burn patients admitted to UNC Jaycee Burn Center. Plasma levels of insulin, insulin-like growth factor 1 (IGF-I) and insulin-like growth factor binding protein 1 (IGGBP-1) were measured on admission up to 10 days post admission. ELISA was used to measure serum levels of insulin, IGF-I and IGFBP-1. Serine phosphorylation of IGFBP-1 was measured by Western blot with and without the incubation of calf intestinal phosphatase (CIP). Significant findings: There was a significant positive correlation of increasing %TBSA burn and increasing levels of serum IGFBP-1 from admittance blood draws. Levels of IGF-I also decreased with increasing Total Body Surface Area (TBSA, p<0.05). In patients studied longitudinally (n=84) we found that IGFBP-1 levels are significantly (p<0.05) increased 1-72 hours post burn (mean±SEM serum concentration; burn=172±23 ng/mL, normal=13±3 ng/mL) and that levels of IGF-I are reduced. IGFBP-1 is serine phosphorylated in burn patients. In patients surviving past 72 hours IGFBP-1 remained phosphorylated over the study period. Conclusions: IGFBP-1 and its serine phosphorylation regulate and limit IGF-I bioavailability. Our results suggest that increases in IGFBP-1 and persistent serine phosphorylation of IGFBP-1 correlate with the severity of burn injury, and may contribute to burn-associated T cell apoptosis and subsequent immune dysfunction by reducing the bioavailability of this important cell survival factor.
机译：目的：烧伤与T细胞的早期凋亡死亡有关。胰岛素样生长因子-1（IGF-1）能够保护T细胞免于凋亡。 IGF-1与其IGFBP（结合蛋白）-1的结合限制了其生物利用度，并且由于对IGF-1的亲和力增加，IGFBP-1的丝氨酸磷酸化进一步降低了其生物利用度。磷酸化的IGFBP-1的水平已显示在小儿烧伤患者中增加。因此，我们假设对烧伤患者进行的纵向研究将证明1）随着时间的推移，IGFBP-1水平升高; 2）IGFBP-1磷酸化水平升高; 3）IGF-1水平降低。方法：我们对UNC Jaycee烧伤中心收治的成人烧伤患者进行了一项前瞻性观察研究。入院后直至入院后10天均测量血浆胰岛素，胰岛素样生长因子1（IGF-1）和胰岛素样生长因子结合蛋白1（IGGBP-1）的血浆水平。 ELISA用于测量胰岛素，IGF-1和IGFBP-1的血清水平。在有或没有孵育小牛肠磷酸酶（CIP）的情况下，通过蛋白质印迹法测量IGFBP-1的丝氨酸磷酸化。重要发现：入院抽血时％TBSA灼伤增加与血清IGFBP-1水平升高呈显着正相关。随着总表面积的增加，IGF-I的水平也降低了（TBSA，p <0.05）。在纵向研究的患者中（n = 84），我们发现烧伤后1-72小时IGFBP-1水平显着增加（p <0.05）（平均值±SEM血清浓度;烧伤= 172±23 ng / mL，正常= 13± 3 ng / mL），并且降低了IGF-I的水平。 IGFBP-1在烧伤患者中被丝氨酸磷酸化。在研究期间存活超过72小时的患者中，IGFBP-1仍被磷酸化。结论：IGFBP-1及其丝氨酸磷酸化调节并限制了IGF-1的生物利用度。我们的结果表明，IGFBP-1的增加和IGFBP-1的持续丝氨酸磷酸化与烧伤的严重程度相关，并可能通过降低该重要细胞存活因子的生物利用度而导致烧伤相关的T细胞凋亡和随后的免疫功能障碍。

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