Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis View Full Text


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Article Info

DATE

2015-10-07

AUTHORS

Minami Sato, Shingo Kuroda, Karima Qurnia Mansjur, Ganzorig Khaliunaa, Kumiko Nagata, Shinya Horiuchi, Toshihiro Inubushi, Yoshiko Yamamura, Masayuki Azuma, Eiji Tanaka

ABSTRACT

IntroductionLow-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.MethodsHuman 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.ResultsTNF-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).ConclusionsThese 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. More... »

PAGES

278

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-015-0798-8

DOI

http://dx.doi.org/10.1186/s13075-015-0798-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023105165

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26445930


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    "description": "IntroductionLow-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 Sj\u00f6gren 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.MethodsHuman salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-\u03b1 (TNF-\u03b1; 10\u00a0ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5\u00a0MHz or 3\u00a0MHz with a spatial average intensity of 30\u00a0mW/cm2 and a pulse rate of 20\u00a0%. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-\u03b1 were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor \u03baB (NF-\u03baB) 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.ResultsTNF-\u03b1 stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p\u2009<\u20090.01), whereas LIPUS treatment abolished them (p\u2009<\u20090.05). The expression changes of AQP5 and TNF-\u03b1 were also inhibited in LIPUS treatment by blocking the NF-\u03baB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-\u03b1 or interleukin 1\u03b2 stimulation (NS-SV-AC, p\u2009<\u20090.01; NS-SV-DC, p\u2009<\u20090.05). 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\u2009<\u20090.01).ConclusionsThese results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-\u03b1 production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-\u03baB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS.", 
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29 schema:description IntroductionLow-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.MethodsHuman 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.ResultsTNF-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).ConclusionsThese 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.
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37 AQP5 expression
38 ConclusionsThese results
39 DC cells
40 LIPUS
41 LIPUS exposure
42 LIPUS treatment
43 MHz
44 MRL/lpr mice
45 NF-κB
46 NF-κB pathway
47 NS-SV
48 Recent studies
49 Sjögren's syndrome
50 TNF
51 TNF-α production
52 Western blot analysis
53 acinar
54 aim
55 analysis
56 aquaporin 5
57 autoimmune sialadenitis
58 average intensity
59 blot analysis
60 bone healing
61 cell number
62 cells
63 changes
64 cm2
65 common symptoms
66 decrease
67 ductal cells
68 effect
69 effectiveness
70 effectiveness of LIPUS
71 exposure
72 expression
73 expression changes
74 factor-κB pathway
75 factors
76 feedback
77 feedback regulator
78 flow
79 fluid secretion rate
80 frequency
81 gland
82 healing
83 increase
84 inflamed salivary glands
85 inflammation
86 inflammatory stimulation
87 inhibitory effect
88 intensity
89 interleukin-1β stimulation
90 lpr mice
91 mRNA expression
92 mW/cm2
93 mice
94 model
95 mouse model
96 necrosis factor
97 negative feedback
98 negative feedback regulator
99 net fluid secretion rate
100 nonthermal effects
101 nuclear factor-κB pathway
102 number
103 pathway
104 production
105 pulse rate
106 pulsed ultrasound signals
107 quality
108 quality of saliva
109 quantity
110 rate
111 regulator
112 response
113 results
114 saliva
115 salivary flow
116 salivary gland acinar
117 salivary glands
118 salivary secretion
119 secretion
120 secretion rate
121 sham exposure
122 sialadenitis
123 signals
124 significant decrease
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126 soft tissue
127 spatial average intensity
128 stimulation
129 strategic therapy
130 study
131 successful treatment
132 symptoms
133 syndrome
134 therapeutic effect
135 therapy
136 tissue
137 treatment
138 tumor necrosis factor
139 ultrasound
140 ultrasound signals
141 upregulate expression
142 xerostomia
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