Shimizu Shino, Ogawa Takao, Seno Satoshi, Kouzaki Hideaki, Shimizu Takeshi
Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
Ann Otol Rhinol Laryngol. 2013 Nov;122(11):683-9. doi: 10.1177/000348941312201104.
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.
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.
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.
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.
炎症的消退是一个由多种抗炎和促消退介质控制的主动过程。脂氧素A4是一种内源性脂质介质,是一种潜在的促消退介质,可减轻炎症。本研究旨在阐明脂氧素A4在上气道炎症中的作用。
收集鼻息肉慢性鼻窦炎患者、过敏性鼻炎患者和对照受试者的鼻分泌物。采用酶联免疫吸附测定法测定脂氧素A4的浓度。在内鼻手术期间从鼻息肉和下鼻甲获取鼻组织。通过逆转录聚合酶链反应检测鼻组织中脂氧合酶(LOXs)、脂氧素受体(甲酰肽受体样1;FPRL-1)和半胱氨酰白三烯1型受体(CysLT1R)的mRNA表达。通过免疫组织化学染色确定FPRL-1的组织定位。还检测了脂氧素A4对气道上皮细胞的体外作用。
在鼻分泌物中发现了显著浓度的脂氧素A4,且过敏性鼻炎患者的浓度升高。鼻息肉中5-LOX、15-LOX-1、FPRL-1和CysLT1R的mRNA表达显著高于下鼻甲。FPRL-1定位于鼻上皮细胞。脂氧素A4通过其受体FPRL-1抑制肿瘤坏死因子α诱导的气道上皮细胞释放白细胞介素8。
这些结果表明脂氧素A4可能在上气道炎症的消退中起作用。低浓度的脂氧素A4可能参与上气道的慢性炎症。