Pro-resolution Mediator Lipoxin A4 and Its Receptor in Upper Airway Inflammation

Objectives: The resolution of inflammation is an active process controlled by several anti-inflammatory and pro-resolution mediators. Lipoxin A4, an endogenous lipid mediator, is a potential pro-resolution mediator that could attenuate inflammation. This study was conducted to elucidate the role of lipoxin A4 in upper airway inflammation. Methods: Nasal secretions were collected from patients with chronic rhinosinusitis with nasal polyposis, patients with allergic rhinitis, and control subjects. The concentration of lipoxin A4 was measured by enzyme-linked immunosorbent assay. Nasal tissues were obtained from nasal polyps and inferior turbinates during endonasal surgery. The mRNA expressions of lipoxygenases (LOXs), lipoxin receptor (formyl peptide receptor like 1; FPRL-1), and cysteinyl leukotriene type 1 receptor (CysLT1R) in nasal tissues were examined by reverse-transcription polymerase chain reaction. Tissue localization of FPRL-1 was determined by immunohistochemical staining. The in vitro effect of lipoxin A4 on airway epithelial cells was also examined. Results: A significant concentration of lipoxin A4 was found in nasal secretions, and the concentration was increased in patients with allergic rhinitis. The mRNA expressions of 5-LOX, 15-LOX-1, FPRL-1, and CysLT1R were significantly greater in nasal polyps than in inferior turbinates. FPRL-1 was localized in nasal epithelial cells. Lipoxin A4 inhibited tumor necrosis factor alpha-induced interleukin 8 release from airway epithelial cells via its receptor FPRL-1. Conclusions: These results indicate that lipoxin A4 may play a role in the resolution of upper airway inflammation. A low concentration of lipoxin A4 may be involved in chronic inflammation of the upper airways.