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低出力パルス超音波は自己免疫疾患での唾液腺炎による唾液分泌低下を改善する
著者
佐藤, 南 徳島大学大学院口腔科学教育部(口腔科学専攻)
マンスル, カリマ クールニア Tokushima University
ハリウナ, ガンゾリブ Tokushima University
永田, 久美子 Tokushima University
犬伏, 俊博 Sanford-Burnham Medical Research Institute
キーワード
Low-intensity pulsed ultrasound
Sjögren syndrome
xerostomia
salivary glands
inflammation
資料タイプ
学位論文
抄録
Introduction: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
掲載誌名
Arthritis Research & Therapy
ISSN
14786362
出版者
Springer nature
17
開始ページ
278
発行日
2015-10-07
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201606141007.pdf
審査要旨 : LID201606141008.pdf
論文本文 : LID201606141009.pdf
本論文は, 著者Minami Satoの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2941号
学位記番号
甲口第406号
学位授与年月日
2016-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
病院