Honda Machiko, Kimura Chiemi, Uede Toshimitsu, Kon Shigeyuki
Department of Molecular Immunology, Faculty of Pharmaceutical Sciences, Fukuyama University, 985, Sanzo, Higashimura-cho, Fukuyama, 729-0292, Japan.
Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan.
J Cell Commun Signal. 2020 Jun;14(2):223-232. doi: 10.1007/s12079-020-00554-7. Epub 2020 Feb 16.
Previously, we reported that an extracellular matrix protein, osteopontin (OPN), is involved in various autoimmune diseases using a neutralizing polyclonal antibody against OPN generated in rabbits. However, the antibody cannot be used for long-term mouse models of chronic inflammatory disease because of the induction of antibodies against anti-OPN rabbit IgG. In this study, we generated a new antibody, anti-mouse OPN mouse IgG (35B6). 35B6 inhibited the cell adhesion of mouse and human OPN to Chinese Hamster Ovary (CHO) cells or CHO cells expressing α4 or α9 integrin. It was reported that OPN is highly expressed and has an important role in a chronic liver disease, non-alcoholic steatohepatitis (NASH). 35B6 injection twice a week for 8 weeks attenuated liver inflammation and fibrosis in a NASH mouse model, suggesting 35B6 is beneficial for the treatment of NASH. 35B6 was preferable to the rabbit anti-OPN antibody for investigating the in vivo function of OPN in mouse models of long-term disease.
此前，我们报道过一种细胞外基质蛋白骨桥蛋白（OPN），利用在兔体内产生的针对OPN的中和多克隆抗体，发现其与多种自身免疫性疾病有关。然而，由于会诱导产生针对抗OPN兔IgG的抗体，该抗体不能用于慢性炎症性疾病的长期小鼠模型。在本研究中，我们制备了一种新的抗体，抗小鼠OPN小鼠IgG（35B6）。35B6抑制小鼠和人OPN与中国仓鼠卵巢（CHO）细胞或表达α4或α9整合素的CHO细胞的细胞黏附。据报道，OPN在慢性肝病非酒精性脂肪性肝炎（NASH）中高表达且起重要作用。在NASH小鼠模型中，每周注射两次35B6，持续8周，可减轻肝脏炎症和纤维化，这表明35B6对NASH的治疗有益。在长期疾病的小鼠模型中研究OPN的体内功能时，35B6比兔抗OPN抗体更具优势。
