Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis.
Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis.
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DOI：
10.1186/s13075-015-0798-8
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发表时间：
2015-10-07
影响因子：
4.9
通讯作者：
Tanaka E
中科院分区：
文献类型：
--
作者：
Sato M;Kuroda S;Mansjur KQ;Khaliunaa G;Nagata K;Horiuchi S;Inubushi T;Yamamura Y;Azuma M;Tanaka E
低强度脉冲超声（LIPUS）已被认为是通过非热效应促进骨愈合。在最近的研究中，LIPUS已被证明可以减少受伤软组织的炎症。口干是干燥综合征（SS）最常见的症状之一。它是由唾液的数量或质量下降引起的。口腔干燥症的成功治疗仍然难以实现，并且常常不令人满意。本研究的目的是阐明LIPUS对SS口干症的治疗作用。在LIPUS或假暴露之前，将人唾液腺腺泡（NS-SV-AC）和导管（NS-SV-DC）细胞与肿瘤坏死因子-α（TNF-α; 10 ng/ml）一起培养或不培养。脉冲超声信号以1.5MHz或3 MHz的频率、30 mW/cm 2的空间平均强度和20%的脉冲率发射。随后分析细胞数量、净液体分泌率以及水通道蛋白5（AQP 5）和TNF-α的表达。Western blot检测LIPUS对核因子κB（NF-κB）通路的抑制作用。还在患有自身免疫性涎腺炎的SS的MRL/MpJ/lpr/lpr（MRL/lpr）小鼠模型中检查了LIPUS在恢复唾液分泌方面的有效性。TNF-α刺激NS-SV-AC和NS-SV-DC细胞导致细胞数量和净液体分泌率显著减少（p < 0.01），而LIPUS处理则使其消失（p < 0.05）。LIPUS可通过阻断NF-κB通路抑制AQP 5和TNF-α表达的变化。此外，我们发现，在TNF-α或白细胞介素1β刺激后，LIPUS处理显著增加了负反馈调节因子A20的mRNA表达（NS-SV-AC，p < 0.01; NS-SV-DC，p < 0.05）。体内LIPUS暴露于MRL/lpr小鼠通过减少唾液腺中的炎症表现出唾液流量和AQP 5表达的显著增加（p < 0.01）。这些结果表明，LIPUS上调AQP 5的表达并抑制TNF-α的产生。因此，LIPUS可以恢复发炎唾液腺的分泌。它可能协同激活NF-κB信号负反馈以响应炎症刺激。LIPUS可能是治疗自身免疫性涎腺炎伴SS患者口干症的一种新的策略。本文的在线版本（doi：10.1186/s13075-015-0798-8）包含补充材料，可供授权用户使用。
Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or quality of saliva. The successful treatment of xerostomia is still difficult to achieve and often unsatisfactory. The aim of this study is to clarify the therapeutic effects of LIPUS on xerostomia in SS. Human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-α (TNF-α; 10 ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5 MHz or 3 MHz with a spatial average intensity of 30 mW/cm2 and a pulse rate of 20 %. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-α were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The effectiveness of LIPUS in recovering salivary secretion was also examined in a MRL/MpJ/lpr/lpr (MRL/lpr) mouse model of SS with autoimmune sialadenitis. TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01). These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-α production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-κB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS. The online version of this article (doi:10.1186/s13075-015-0798-8) contains supplementary material, which is available to authorized users.