LIPUS suppressed LPS-induced IL-1 alpha through the inhibition of NF-kappa B nuclear translocation via AT1-PLC beta pathway in MC3T3-E1 cells

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

来源：Journal of Cellular Physiology, 2017, 232(12): 3337-3346.

DOI：10.1002/jcp.25777

• AT1
• IL-1 alpha
• low-intensity pulsed ultrasound
• NF-kappa B
• PLC beta

Inflammatory cytokines, interleukin (IL)-1, IL-6, and TNF-alpha, 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-1 alpha 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-1 alpha 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-1 alpha. LIPUS also reduced the nuclear translocation of NF-kappa B by LPS-induced IL-1 alpha. Losartan and siAT1 blocked all the stimulatory effects of LIPUS on IL-1a production and IL-1 alpha-mediated NF-kappa B translocation induced by LPS. Furthermore, PLC beta inhibitor U73122 recovered NF-kappa B translocation. These results suggest that LIPUS inhibits LPS-induced IL-1 alpha via AT1-PLC beta in osteoblasts. We exhibit that these findings are in part of the signaling pathway of LIPUS on the anti-inflammatory effects of IL-1a expression.

• 出版日期2017-12