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，但烧伤后愈合不良仍然是一个主要问题。受损 愈合与感染的风险增加以及住院时间延长和费用昂贵有关。因此，在本发明中， 描述控制伤口愈合的特定机制是烧伤研究中的一个可怕的目标。 在这里，我们提出，激活5-脂氧合酶（5-LO）途径，在受影响的网站是一个先前的 不受重视的机制，管弦乐队烧伤伤口愈合。5-LO介导白三烯的合成 (LTs)，一组来自花生四烯酸的脂质介质。LT由白三烯B4（LTB 4）和 半胱氨酰白三烯（cysLT），并且都以其促炎功能而闻名。然而，受监管的LT 活性可能在正常组织功能和修复中起作用。 我们的初步数据表明，5-LO途径是活跃的烧伤伤口部位。有趣的是，我们的数据显示， LTB 4和cysLTs在烧伤创面愈合中发挥相反的功能。这项研究旨在剖析 5-LO活性协调烧伤后愈合的机制。此外，我们将研究 假设损伤后早期伤口部位5-LO/LTB 4活性升高与损伤相关， 烧伤病人的康复 成功完成这一提案将对新的治疗策略的发展产生影响 对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.