Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling.
Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling.
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DOI：
10.1111/j.1600-0714.2012.01181.x
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Deshmukh US
中科院分区：
文献类型：
--
作者：
Nandula SR;Dey P;Corbin KL;Nunemaker CS;Bagavant H;Deshmukh US
通过聚肌胞苷酸（poly（I：C））激活先天免疫导致急性唾液腺功能减退。由于poly（I：C）治疗的主要结果是I型干扰素（IFN）的产生，本研究旨在研究它们在唾液腺功能障碍中的作用。用poly（I：C）处理不同品系的小鼠，这些小鼠缺乏干扰素α受体（IFNAR 1 −/−）、IL-6−/−、IL-10−/−或EBI 3 −/−。通过测量毛果芸香碱诱导的唾液体积来确定唾液腺功能。通过真实的时间PCR测量基因表达水平。使用离体腺泡细胞进行Ca 2+动员研究。单次注射聚（I：C）在野生型B6小鼠中迅速诱导唾液腺功能减退（与PBS处理的小鼠相比，唾液体积下降41%）。相比之下，poly（I：C）治疗的IFNAR−/−小鼠的功能丧失仅为9.6%。基因表达分析显示，在poly（I：C）处理的IFNAR−/−小鼠的颌下腺中，IL-6、IL-10和IL-27的水平降低。虽然poly（I：C）处理的IL-10−/−和EBI 3 −/−小鼠的唾液腺功能障碍与野生型小鼠相当，但IL-6−/−小鼠更具抗性，功能仅下降21%。毛果芸香碱诱导的Ca 2+流量显着抑制腺泡细胞从聚（I：C）治疗的野生型小鼠。我们的数据表明，I型IFN和IL-6的联合作用导致唾液腺功能减退。这通过干扰腺泡细胞内的Ca 2+动员而发生。因此，在急性病毒感染和干燥综合征等疾病中，I型IFN和IL-6水平升高可直接影响腺体功能。
Activation of innate immunity through polyinosinic:polycytidylic acid (poly(I:C)) causes acute salivary gland hypofunction. Since a major consequence of poly(I:C) treatment is type I interferon (IFN) production, this study was undertaken to investigate their role in salivary gland dysfunction. Different strains of mice, deficient either in interferon alpha receptor (IFNAR1−/−), or IL-6−/−, or IL-10−/−, or EBI3−/− were treated with poly(I:C). Salivary gland function was determined by measuring pilocarpine induced saliva volume. Gene expression levels were measured by real time PCR. Ca2+ mobilization studies were done using ex-vivo acinar cells. A single injection of poly(I:C) rapidly induced salivary gland hypofunction in wild type B6 mice (41% drop in saliva volumes compared to PBS treated mice). In contrast, the loss of function in poly(I:C) treated IFNAR−/− mice was only 9.6%. Gene expression analysis showed reduced levels of Il-6, Il-10 and Il-27 in submandibular glands of poly(I:C) treated IFNAR−/− mice. While salivary gland dysfunction in poly(I:C) treated IL-10−/− and EBI3−/− mice was comparable to wild type mice, the IL-6−/− mice were more resistant, with only a 21 % drop in function. Pilocarpine induced Ca2+ flux was significantly suppressed in acinar cells obtained from poly(I:C) treated wild type mice. Our data demonstrates that a combined action of type I IFNs and IL-6 contributes towards salivary gland hypofunction. This happens through interference with Ca2+ mobilization within acinar cells. Thus, in acute viral infections and diseases like Sjögren’s syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function.
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DOI：
10.1111/j.1600-0714.2008.00700.x
发表时间：
2009-01
期刊：
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
影响因子：
--
作者：
Deshmukh US;Nandula SR;Thimmalapura PR;Scindia YM;Bagavant H
通讯作者：
Bagavant H
影响因子：
3.4
作者：
Camargo Grossmann, Soraya de Mattos;Teixeira, Rosangela;Vieira do Carmo, Maria Auxiliadora
通讯作者：
Vieira do Carmo, Maria Auxiliadora
影响因子：
3.8
作者：
Kasman, L. M.;London, L. L.;Pilgrim, M. J.
通讯作者：
Pilgrim, M. J.
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
影响因子：
5.4
作者：
Ittah, Marc;Miceli-Richard, Corinne;Mariette, Xavier
通讯作者：
Mariette, Xavier