5-Lipoxygenase Knockout Aggravated Apical Periodontitis in a Murine Model.

5-Lipoxygenase (5-LO) plays a vital role in the host innate immune response, including bacteria-induced inflammation. Apical periodontitis (AP) is due to immune disorders caused by imbalances between bacterial invasion and subsequent host defense response. In this work, we investigated the role of 5-lipoxygenase in AP by using 5-lo knockout mice (5-lo-/- mice). Results showed that 5-lo-/- mice had greater periapical bone loss and more osteoclasts positive for tartrate-resistant acid phosphatase staining than did wild-type mice, as determined by micro-computed tomography and histologic staining. The inflammation- and osteoclastogenesis-related factors IL-beta, TNF-alpha, RANK, and RANKL were also significantly elevated in 5-lo-/- mice, whereas osteoprotegerin was reduced. Furthermore, peritoneal macrophages from 5-lo-/- mice revealed an obviously impaired ability to phagocytose the AP pathogenic bacteria Fusobacterium nucleatum. In vivo experiments confirmed that 5-lo knockout led to decreased macrophage recruitment and increased F. nucleatum infection around the periapical area due to decreased leukotriene B-4 and LXA4 production. All these results showed that 5-lo knockout impaired the host innate immune system to promote the release of bone resorption-related factors. Therefore, 5-lo deficiency aggravated AP in an experimental murine AP model.