High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells
High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells
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DOI：
10.1007/s00262-008-0584-4
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发表时间：
2009-04-01
影响因子：
5.8
通讯作者：
Delvenne, Philippe
中科院分区：
文献类型：
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作者：
Herfs, Michael;Herman, Ludivine;Delvenne, Philippe
虽然在大多数宫颈鳞状上皮内病变（SIL）和宫颈癌（SCC）中检测到人乳头瘤病毒（HPV）DNA，但宫颈病变的持续或进展表明病毒抗原未充分呈递给免疫系统。大多数SIL显示朗格汉斯细胞（LC）的数量和功能改变，这一观察结果加强了这一假设。本研究的目的是确定是否甘草素（PG）可能会影响LC密度在宫颈（前）肿瘤上皮。我们首先证实了PGE（2）酶途径，包括环氧合酶-2（考克斯-2）和微粒体前列腺素E合成酶1（mPGES-1）的上皮表达在SIL和SCC中高于正常外分泌上皮，并且与CD 1a阳性LC的密度呈负相关。通过使用细胞迁移试验，我们接下来表明，未成熟树突状细胞（DC）和在PGE（2）存在下体外部分分化的DC的运动性受到PGE（2）的不同影响。与在PGE（2）存在下体外产生的DC相比，未成熟DC在PGE（2）存在下具有较低的迁移能力。最后，我们发现PGE（2）诱导了细胞因子的产生和耐受性DC的表型特征，表明PGE（2）酶途径的表达改变可能通过促进（前）癌免疫耐受而促进宫颈癌的发生。
Although human papillomavirus (HPV) DNA is detected in the majority of squamous intraepithelial lesions (SIL) and carcinoma (SCC) of the uterine cervix, the persistence or progression of cervical lesions suggest that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most SIL show quantitative and functional alterations of Langerhans cells (LC). The aim of this study was to determine whether prostaglandins (PG) may affect LC density in the cervical (pre)neoplastic epithelium. We first demonstrated that the epithelial expression of PGE(2) enzymatic pathways, including cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1), is higher in SIL and SCC compared to the normal exocervical epithelium and inversely correlated to the density of CD1a-positive LC. By using cell migration assays, we next showed that the motility of immature dendritic cells (DC) and DC partially differentiated in vitro in the presence of PGE(2) are differentially affected by PGE(2). Immature DC had a lower ability to migrate in the presence of PGE(2) compared to DC generated in vitro in the presence of PGE(2). Finally, we showed that PGE(2) induced a cytokine production profile and phenotypical features of tolerogenic DC, suggesting that the altered expression of PGE(2) enzymatic pathways may promote the cervical carcinogenesis by favouring (pre)cancer immunotolerance.