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.
