5-Lipoxygenase exerts dual and opposing functions during the wound healing process

尽管在护理方面取得了重大进展，但烧伤后愈合受损仍然是一个主要问题。受损的 治愈与感染风险增加和长时间且昂贵的住院期有关。因此， 描述控制创面愈合的具体机制是烧伤研究中的一个可怕目标。 在这里，我们认为5-脂氧合酶(5-LO)途径在受影响部位的激活是先前的 不为人知的兰花烧伤创面愈合机制。5-LO介导白三烯的合成 (LTS)，一组源于花生四烯酸的脂质调节剂。它由白三烯B4(LTB4)和 半胱氨酰白三烯(CysLts)，并都以其促炎功能而闻名。然而，受监管的LT 活动可能在正常的组织功能和修复中发挥作用。 我们的初步数据显示，5-LO通路在烧伤创面处是活跃的。有趣的是，我们的数据表明 LTB4和cysLts在烧伤创面愈合过程中发挥相反的作用。这项研究旨在剖析 5-LO活性协调烧伤后愈合的机制。此外，我们还将研究 创伤后早期伤口部位5-LO/LTB4活性升高的假说与损伤有关 烧伤病人的治愈。 这项提议的成功完成将对开发新的治疗策略产生影响 适用于无法愈合的烧伤患者。

Despite significant advances in care, impaired healing after burn injury still remains a major concern. Impaired healing is associated with increased risk for infections and prolonged and costly hospitalization periods. Thus, delineation of specific mechanisms that govern wound healing is a dire objective in burn injury research. Here, we propose that activation of the 5-Lipoxygenase (5-LO) pathway at the affected site is a previously unappreciated mechanism that orchestraes burn wound healing. 5-LO mediates the synthesis of leukotrienes (LTs), a team of lipid mediators that derive from arachidonic acid. LTs consist of leukotriene B4 (LTB4) and the cysteinyl leukotrienes (cysLTs), and are all known for their proinflammatory functions. However, regulated LT activity may play roles in normal tissue function and repair. Our preliminary data show that the 5-LO pathway is active at the burn wound site. Interestingly our data suggest that LTB4 and cysLTs exert opposing functions in burn wound healing. This study is designed to dissect the mechanisms by which 5-LO activity orchestrates healing after burn injury. Furthermore, we will examine the hypothesis that heightened 5-LO/LTB4 activity at the wound site early after injury is associated with impaired healing in burn patients. Successful completion of this proposal will have implications on the development of new therapeutic strategies for patients with non-healing burn injuries.