オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Alendronate attenuates eosinophilic airway inflammation associated with suppression of Th2 cytokines, Th17 cytokines, and eotaxin-2.
掲載誌名	正式名：Journal of immunology (Baltimore, Md. : 1950) ISSNコード：0022-1767
掲載区分	国外
出版社	AMER ASSOC IMMUNOLOGISTS
巻・号・頁	191(6),pp.2879-89
著者・共著者	Oh Sasaki,Mitsuru Imamura,Yusuke Yamazumi,Hiroaki Harada,Taku Matsumoto,Katsuhide Okunishi,Kazuyuki Nakagome,Ryoichi Tanaka,Tetsu Akiyama,Kazuhiko Yamamoto,Makoto Dohi
発行年月	2013/09/15
概要	Bisphosphonates (BPs) have been widely used to treat osteoporosis. They act by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. This resembles the action of statins, whose immune-modulating effect has recently been highlighted. In contrast, the effect of BPs on immune responses has not been elucidated well. In this study, we examined the effect of alendronate (ALN), a nitrogen-containing BP, on allergic airway inflammation in a mouse model. BALB/c mice were sensitized twice with OVA and challenged three times with nebulized OVA to induce eosinophilic airway inflammation. ALN was administered by an intragastric tube before each inhalation. ALN strongly suppressed airway eosinophilia and Th2, as well as Th17 cytokine production in the lung. ALN also attenuated eotaxin-2 production in the lung. Immunohistochemistry demonstrated that the major cell source of eotaxin-2 was peribronchial/perivascular macrophages, and flow cytometrical studies confirmed that ALN decreased eotaxin-2 expression in these macrophages. Furthermore, ALN attenuated eotaxin-2 production from mouse pleural macrophages and human monocyte/macrophage-like THP-1 cells in vitro. These results suggest that ALN suppressed Ag-induced airway responses in the mouse model. The suppression of eotaxin-2 production from macrophages appears to be one of ALN's immunomodulatory effects, whereas the mechanism by which ALN suppressed Th2 and Th17 responses could not be fully elucidated in this study. Although a clinical study should be conducted, ALN could be a novel therapeutic option for asthma.
DOI	10.4049/jimmunol.1300460
PMID	23935198