title: LIPUS suppressed LPS-induced IL-1α through the inhibition of NF-κB nuclear translocation via AT1-PLCβ pathway in MC3T3-E1 cells.
abstract: 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.
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Biochemistry, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Division of Advanced Dental Treatment, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Natsuko
authors.identifier: http://orcid.org/0000-0002-6339-0785
authors.initials: N
authors.lastname: Tanabe
authors.affiliation: Department of Periodontology, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Manaka
authors.affiliation: Division of Advanced Dental Treatment, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Department of Anatomy, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Naito
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sekino
authors.affiliation: Department of Periodontology, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Division of Functional Morphology, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Division of Advanced Dental Treatment, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Department of Oral Health Sciences, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawato
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Torigoe
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Kato
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tsukune
authors.affiliation: Division of Advanced Dental Treatment, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Department of Oral Health Sciences, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
authors.affiliation: Department of Biochemistry, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Division of Advanced Dental Treatment, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Periodontology, Nihon University Graduate School of Dentistry, Tokyo, Japan.|Division of Functional Morphology, Dental Research Center, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D053582:Interleukin-1alpha / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D054799:Phospholipase C beta / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000069453:Ultrasonic Waves
chemical_list: D053582:Interleukin-1alpha; D008070:Lipopolysaccharides; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D054799:Phospholipase C beta
keywords: AT1; IL-1α; NF-κB; PLCβ; low-intensity pulsed ultrasound