Activation of innate immune responses through Toll-like receptor 3 causes a rapid loss of salivary gland function.
Activation of innate immune responses through Toll-like receptor 3 causes a rapid loss of salivary gland function.
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DOI：
10.1111/j.1600-0714.2008.00700.x
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Bagavant H
中科院分区：
文献类型：
--
作者：
Deshmukh US;Nandula SR;Thimmalapura PR;Scindia YM;Bagavant H
最近的研究表明，Toll样受体3（TLR 3）表达的唾液腺和上皮细胞系来源于干燥综合征（SS）患者。由于病毒感染被认为是SS的触发因素，因此在本研究中我们研究了TLR 3的体内参与是否影响唾液腺功能。雌性NZB/WF 1小鼠反复注射聚肌胞苷酸（poly（I：C））。免疫组化法检测TLR 3在下颌下腺的表达。采用真实的时间PCR法检测颌下腺炎性细胞因子的RNA水平。毛果芸香碱诱导的唾液量被用作腺体功能的指标。免疫组化结果显示，TLR 3在颌下腺的浆液性腺泡、粘液性腺泡、颗粒曲小管和导管上皮中均有表达。Poly（I：C）处理迅速上调I型IFN和炎性细胞因子在下颌下腺中的mRNA水平。治疗后一周，与PBS治疗的小鼠相比，聚（I：C）治疗的小鼠的唾液体积显著减少。苏木素和伊红染色显示唾液腺组织学正常，未检测到淋巴细胞灶。停止聚（I：C）治疗后，腺体功能恢复。我们的研究结果表明，TLR 3在唾液腺内的参与导致腺体功能的快速丧失。这种现象与唾液腺中I型IFN和炎性细胞因子的产生有关。腺功能的恢复表明，SS的病毒病因，唾液腺的慢性感染可能是必要的。
Recent studies have demonstrated the expression of Toll-like receptor 3 (TLR3) in salivary glands and epithelial cell lines derived from Sjögren’s syndrome (SS) patients. Since viral infections are considered to be a trigger for SS, in this study we investigated whether in vivo engagement of TLR3 affects salivary gland function. Female NZB/WF1 mice were repeatedly injected with polyinosinic:polycytidylic acid (poly(I:C)). TLR3 expression within submandibular glands was studied by immunohistochemistry. RNA levels of inflammatory cytokines in the submandibular glands were determined by real time PCR. Pilocarpine induced saliva volume was used as an index of glandular function. Immunohistochemical analysis of submandibular glands showed TLR3 expression in epithelium of serous and mucous acini, granular convoluted tubules and ducts. Poly(I:C) treatment rapidly upregulated the mRNA levels of type I IFN and inflammatory cytokines in the submandibular glands. By one week after treatment, the saliva volumes in poly(I:C) treated mice were significantly reduced in comparison with the PBS treated mice. Hematoxylin and eosin staining showed that salivary gland histology was normal and lymphocytic foci were not detected. Glandular function recovered after poly(I:C) treatment was stopped. Our results demonstrate that engagement of TLR3 within the salivary glands results in a rapid loss of glandular function. This phenomenon is associated with the production of type I IFN and inflammatory cytokines in the salivary glands. Restoration of glandular function suggests that for viral etiology of SS, a chronic infection of salivary glands might be necessary.
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影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
5.4
作者：
Ittah, Marc;Miceli-Richard, Corinne;Mariette, Xavier
通讯作者：
Mariette, Xavier
影响因子：
4.6
作者：
Spachidou, M. P.;Bourazopoulou, E.;Manoussakis, M. N.
通讯作者：
Manoussakis, M. N.
影响因子：
3.4
作者：
Zoukhri, Driss;Macari, Elizabeth;Kublin, Claire L.
通讯作者：
Kublin, Claire L.
DOI：
10.1196/annals.1422.046
发表时间：
2007-01-01
期刊：
AUTOIMMUNITY, PT D
影响因子：
--
作者：
Jonsson, Roland;Bolstad, Anne Isine;Brun, Johan G.
通讯作者：
Brun, Johan G.