Expression of functional Toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjogren's syndrome
Expression of functional Toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjogren's syndrome
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DOI：
10.1111/j.1365-2249.2006.03311.x
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发表时间：
2007-03-01
影响因子：
4.6
通讯作者：
Manoussakis, M. N.
中科院分区：
文献类型：
--
作者：
Spachidou, M. P.;Bourazopoulou, E.;Manoussakis, M. N.
Toll样受体（TLR）在先天性和适应性免疫应答的激活中起重要作用。唾液腺上皮细胞（SGEC）可能参与原发性干燥综合征（pSS）特征性腺体炎症反应的发展。在这项研究中，我们试图评估几种TLR分子在培养的非肿瘤性SGEC中的表达和功能，这些SGEC是从pSS患者和疾病对照中获得的。通过逆转录-聚合酶链反应（RT-PCR）分析和定量实时PCR检测pSS患者（SS-SGEC）和疾病对照（对照-SGEC）以及单核细胞系THP-1（阳性对照细胞系）来源的长期培养的非肿瘤性SGEC中TLR 1、TLR 2、TLR 3和TLR 4分子的mRNA表达。通过用TLR配体：金黄色葡萄球菌肽聚糖（TLR 2）、合成dsRNA类似物聚肌苷酸：胞苷酸（TLR 3）和大肠杆菌脂多糖（TLR 4）处理后诱导免疫调节分子CD 54/细胞间粘附分子-1（ICAM-1）、CD 40、CD 86/B7.2、主要组织相容性复合物（MHC）I类和MHC II类的表达（流式细胞术）来评估TLR功能。发现SGEC表达功能性TLR 2、TLR 3和TLR 4分子，如用相应TLR配体处理后表面ICAM-1、CD 40和MHC-I表达（以及相互TLR mRNA）的剂量依赖性上调所证实的。与对照SGEC相比，SS-SGEC系显示TLR 1（P = 0.0027）、TLR 2（P = 0.01）和TLR 4（P = 0.03）mRNA的组成型表达显著更高。这项研究表明，培养的SGEC表达功能性TLR分子; SS-SGEC的高组成性TLR表达可能提示pSS中上皮细胞的内在激活，并进一步支持这种类型的组织在疾病发病机制中的作用。
Toll-like receptors (TLR) play an essential role in the activation of both innate and adaptive immune responses. Salivary gland epithelial cells (SGEC) may participate in the development of glandular inflammatory reactions that characterize primary Sjogren's syndrome (pSS). In this study we sought to assess the expression and function of several TLR molecules in cultured non-neoplastic SGEC obtained from pSS patients and disease controls. Long-term cultured non-neoplastic SGEC derived from pSS patients (SS-SGEC) and disease controls (control-SGEC), as well as the monocytic cell line THP-1 (positive control cell line), were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis and quantitative real-time PCR for mRNA expression of TLR1, -2, -3 and -4 molecules. TLR function was assessed by the induction of the expression (flow cytometry) of the immunoregulatory molecules CD54/intercellular adhesion molecule-1 (ICAM-1), CD40, CD86/B7.2, major histocompatibility complex (MHC) class I and MHC class II following treatment with the TLR ligands: Staphylococcus aureus peptidoglycan (TLR2), the synthetic dsRNA analogue polyinosinic:cytidylic acid (TLR3) and Escherichia coli lipopolysaccharide (TLR4). SGEC were found to express functional TLR2, -3 and -4 molecules, as attested by dose-dependent up-regulation of surface ICAM-1, CD40 and MHC-I expression (as well as of reciprocal TLR mRNA) following treatment with the respective TLR-ligands. SS-SGEC lines displayed significantly higher constitutive expression of TLR1 (P = 0.0027), TLR2 (P = 0.01) and TLR4 (P = 0.03) mRNA compared to control-SGEC. This study demonstrates that cultured SGEC express functional TLR molecules; the high constitutive TLR expression by SS-SGEC is probably suggestive of the intrinsic activation of epithelial cells in pSS and further supports the role of this type of tissue in pathogenesis of the disorder.