Park Se Jin, Jun Young Joon, Lee Ki Jeong, Hwang Soo Min, Kim Tae Hoon, Lee Seung Hoon, Lee Sang Hag
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Hallym University, Chuncheon, Korea.
Am J Rhinol Allergy. 2014 May-Jun;28(3):199-207. doi: 10.2500/ajra.2014.28.4032.
Chronic sinusitis with nasal polyps (CRSwNPs) or CRS without NPs (CRSsNPs) is associated with expression of various cytokines. Lysophosphatidic acid (LPA) generated by autotaxin (ATX), LPA-producing enzyme, initiates signaling cascade involved in the inflammatory responses and participates in diverse biological processes through LPA receptors, including cytokine production. We analyzed the expression and distribution patterns of LPA-related molecules in nasal secretion and sinus mucosa of normal controls and patients with CRSwNPs and CRSsNPs, to evaluate the possible effects of the ATX-LPA receptor axis on the pathogenesis of CRS.
LPA levels in nasal secretion and the expression and distribution patterns of ATX and LPA receptors 1-3 (LPA1-3) in sinus mucosa were investigated using ELISA, real-time polymerase chain reaction, Western blot, and immunohistochemistry. We elucidated the effect of CRS-relevant cytokines on the expression of ATX and LPA receptors, using cultured sinus epithelial cells, and investigated the effect of LPA on the expression of CRS-relevant cytokines, using sinus mucosa explant culture.
LPA, ATX, and LPA1-3 levels are increased in CRSwNPs and CRSsNPs. ATX and LPA1-3 were localized to superficial epithelium, submucosal glands in normal and inflammatory mucosa, but in inflammatory mucosa, they were found in inflammatory cells. LPA1-3 were noted in endothelium. Sinus mucosa explant stimulated with LPA increasingly produced IL-4, IL-5, interferon gamma, and TNF-alpha, and in cultured epithelial cells stimulated with CRS-relevant cytokines, ATX, and LPA1-3 were differentially induced.
LPA in human sinus mucosa may play important roles in the pathogenesis of CRS, contributing to produce CRS-related cytokines. LPA-related molecules were increased in CRS, which may attribute to CRS-related cytokines.
伴有鼻息肉的慢性鼻窦炎（CRSwNPs）或不伴有鼻息肉的慢性鼻窦炎（CRSsNPs）与多种细胞因子的表达有关。由自分泌运动因子（ATX）（一种产生溶血磷脂酸（LPA）的酶）产生的LPA启动参与炎症反应的信号级联，并通过LPA受体参与多种生物学过程，包括细胞因子的产生。我们分析了正常对照者以及CRSwNPs和CRSsNPs患者鼻分泌物和鼻窦黏膜中LPA相关分子的表达和分布模式，以评估ATX-LPA受体轴对CRS发病机制的可能影响。
采用酶联免疫吸附测定（ELISA）、实时聚合酶链反应、蛋白质免疫印迹法和免疫组织化学法，研究鼻分泌物中的LPA水平以及鼻窦黏膜中ATX和LPA受体1-3（LPA1-3）的表达和分布模式。我们使用培养的鼻窦上皮细胞阐明CRS相关细胞因子对ATX和LPA受体表达的影响，并使用鼻窦黏膜外植体培养研究LPA对CRS相关细胞因子表达的影响。
CRSwNPs和CRSsNPs中LPA、ATX和LPA1-3水平升高。ATX和LPA1-3定位于正常和炎性黏膜的浅表上皮、黏膜下腺，但在炎性黏膜中，它们存在于炎性细胞中。在内皮细胞中发现了LPA1-3。用LPA刺激的鼻窦黏膜外植体产生白细胞介素-4、白细胞介素-5、γ干扰素和肿瘤坏死因子-α的量增加，在用CRS相关细胞因子刺激的培养上皮细胞中，ATX和LPA1-3受到不同程度的诱导。
人鼻窦黏膜中的LPA可能在CRS发病机制中起重要作用，有助于产生CRS相关细胞因子。CRS中LPA相关分子增加，这可能归因于CRS相关细胞因子。
