LIPUS suppressed LPS-induced IL-1α through the inhibition of NF-κB nuclear translocation via AT1-PLCβ pathway in MC3T3-E1 cells

Mayu Nagao, Natsuko Tanabe, Soichiro Manaka, Masako Naito, Jumpei Sekino, Tadahiro Takayama, Takayuki Kawato, Go Torigoe, Shunichiro Kato, Naoya Tsukune, Masao Maeno, Naoto Suzuki, Shuichi Sato

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33 Citations (Scopus)


Inflammatory cytokines, interleukin (IL)-1, IL-6, and TNF-α, are involved in inflammatory bone diseases such as rheumatoid osteoarthritis and periodontal disease. Particularly, periodontal disease, which destroys alveolar bone, is stimulated by lipopolysaccharide (LPS). Low-intensity pulsed ultrasound (LIPUS) is used for bone healing in orthopedics and dental treatments. However, the mechanism underlying effects of LIPUS on LPS-induced inflammatory cytokine are not well understood. We therefore aimed to investigate the role of LIPUS on LPS-induced IL-1α production. Mouse calvaria osteoblast-like cells MC3T3-E1 were incubated in the presence or absence of LPS (Porphyromonas gingivalis), and then stimulated with LIPUS for 30 min/day. To investigate the role of LIPUS, we determined the expression of IL-1α stimulated with LIPUS and treated with an angiotensin II receptor type 1 (AT1) antagonist, Losartan. We also investigate to clarify the pathway of LIPUS, we transfected siRNA silencing AT1 (siAT1) in MC3T3-E1. LIPUS inhibited mRNA and protein expression of LPS-induced IL-1α. LIPUS also reduced the nuclear translocation of NF-κB by LPS-induced IL-1α. Losartan and siAT1 blocked all the stimulatory effects of LIPUS on IL-1α production and IL-1α-mediated NF-κB translocation induced by LPS. Furthermore, PLCβ inhibitor U73122 recovered NF-κB translocation. These results suggest that LIPUS inhibits LPS-induced IL-1α via AT1-PLCβ in osteoblasts. We exhibit that these findings are in part of the signaling pathway of LIPUS on the anti-inflammatory effects of IL-1α expression.

Original languageEnglish
Pages (from-to)3337-3346
Number of pages10
JournalJournal of Cellular Physiology
Issue number12
Publication statusPublished - Dec 2017


  • AT1
  • IL-1α
  • NF-κB
  • PLCβ
  • low-intensity pulsed ultrasound


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