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.