Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.

Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.
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DOI:
10.1016/j.bbi.2009.03.006
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发表时间:
2009-08
影响因子:
15.1
通讯作者:
Marucha, Phillip T.
Marucha, Phillip T.
中科院分区:
医学1区
文献类型:
--
作者:
Sroussi, Herve Y.;Williams, Richard L.;Zhang, Qing L.;Villines, Dana;Marucha, Phillip T.

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虽然伤口愈合通常是一个成功的,精心策划和进化的过程,但它可能会受到心理压力等外在因素的影响。在皮肤伤口愈合的SKH-1束缚应激模型中,应激小鼠的伤口闭合速率约慢30%。愈合延迟与伤口部位急性炎症加剧和细菌清除不足有关。在小鼠SKH-1模型中,伤口缺氧可能是导致皮肤伤口愈合受损的机制。皮肤伤口的最佳愈合是逐步修复程序。在其早期阶段,观察到由中性粒细胞产生的炎性氧化爆发。40%的中性粒细胞胞质蛋白质重量由两种钙结合蛋白S100 A8和S100 A9组成。我们之前的工作表明,S100 A8在体外充当人类中性粒细胞的氧化敏感排斥剂。Ala 42 S100 A8是一种定点突变蛋白,对氧化抑制具有抗性,并在体内抑制中性粒细胞募集。因此,我们测试了S100 A8可以改善该模型中的伤口愈合的假设。我们检查了野生型和ala 42 S100 A8改善伤口闭合率的能力的效果。数据表明,ala 42 S100 A8的单次局部应用改善了由应力引起的伤口闭合速率降低。这种情况发生时不会显著影响伤口细菌清除。野生型S100 A8仅对伤口闭合率具有部分有益作用。这些发现支持基于S100的干预以改善受损伤口愈合的进一步转化研究。
Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation sensitive repellent of human neutrophils in-vitro. Ala42S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild type and ala42S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala42S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing.
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