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. Keywords Osteopontin . Antibody . Non-alcoholic steatohepatitis in mice . Inflammation . Fibrosis Abbreviations CDAHFD 0.1% methionine on a high fat diet background col1a1 type I collagen α1 chain CHO Chinese Hamster Ovary ECM extracellular matrix HE hematoxylin-eosin HSC hepatic stellate cells RGD arginine-glycine-aspartate NAFLD non-alcoholic fatty liver disease NASH non-alcoholic steatohepatitis in mice OPN osteopontin SMA smooth muscle actin
Silicosis is a typical form of pneumoconiosis and is characterized as a type of lung fibrosis. Silica particles are captured and recognized upon by alveolar macrophages via the macrophage receptor with collagenous structure (MARCO) scavenger receptor, and thereafter the inflammasome is activated. Thereafter, various chemokines/cytokines play their roles to eventually form fibrosis. Additionally, silica particles chronically activate T helper cells which sets the background for the formation of silicosis-associated autoimmune disturbances. The occurrence and progression of lung fibrosis, the extracellular matrix-related molecules such as integrins and their ligands including fibronectin, vitronectin, laminin, and collagens, all play important roles. Here, the roles of these molecules in silicosis-related lung fibrosis are reviewed from the literature. Additionally, the measurement of serum nephronectin (Npnt), a new member of the integrin family of ligands, is discussed, together with investigations attempting to delineate the role of Npnt in silica-induced lung fibrosis. Serum Npnt was found to be higher in silicosis patients compared to healthy volunteers and seems to play a role in the progression of fibrosis with other cytokines. Therefore, serum Npnt levels may be employed as a suitable marker to monitor the progression of fibrosis in silicosis patients.
The extracellular matrix protein nephronectin (Npnt) is known to be critical for kidney development, but its function in inflammatory diseases is unknown. Here, we developed a new enzyme‐linked immunosorbent assay system to detect Npnt in various autoimmune diseases, which revealed that plasma Npnt levels are increased in various mouse autoimmune models. We also report that antibodies against the α8β1 integrin‐binding region of Npnt protect mice from anti‐type II collagen‐induced arthritis, suggesting that Npnt may be a potential therapeutic target molecule for the prevention of autoimmune arthritis.
Blood levels of the extracellular matrix protein nephronectin (Npnt), a protein critical for kidney development, are elevated in autoimmune experimental encephalitis (EAE) mice, which are a model for multiple sclerosis. We found here that treatment with anti-Npnt antibody directed against the α8β1 integrin-binding site (Npnt-FD antibody) inhibits EAE development. The selenium transporter selenoprotein P (SeP) was identified as a novel Npnt-binding partner. In EAE, Npnt induced SeP and glutathione peroxidase 1 (GPx1) expression, followed by reactive oxygen species (ROS) inhibition in CD4+ T cells; these changes were disturbed by Npnt-FD antibody treatment, which also caused decreased differentiation of interleukin (IL)-17-producing CD4+ T-helper cells (Th17s) and increased differentiation of regulatory T cells (Tregs). Treatment of EAE mice with the ROS scavenger N-acetyl cysteine (NAC) blocked the Npnt-FD antibody-induced decrease in Th17 differentiation and increase in Treg differentiation. In conclusion, the interaction between Npnt and SeP contributes to EAE development by regulating the Th17/Treg balance via the ROS level.
A Case of the activities in Mihara cityIt has been becoming increasingly important to apply geographic information system (GIS) for recognizing, understanding and sharing the spatial conditions in disaster responses. This study aims at obtaining basic information for realizing effective disaster responses through the information support activity using GIS in the disaster volunteer center (VC). Results show that GIS is useful tool for understanding, sharing and managing the information and the complicated analysis on GIS is not necessary in disaster responses.It has been becoming increasingly important to apply geographic information system (GIS) for recognizing, understanding and sharing the spatial conditions in disaster responses. This study aims at obtaining basic information for realizing effective disaster responses through the information support activity using GIS in the disaster volunteer center (VC). Results show that GIS is useful tool for understanding, sharing and managing the information and the complicated analysis on GIS is not necessary in disaster responses. 1.はじめに平成 30 年 6 月 28 日から 7 月 8 日にかけて、台風 7 号および梅雨 前線が引き起こした集中的な豪雨により、西日本を中心に全国各地 で甚大な被害がもたらされた(平成 30 年 7 月豪雨) 。内閣府による と、死者 224 名(14 都道府県) 、行方不明者 8 名(2 県) 、重傷者 109 名、負傷者 318 名(19 都道府県) 、住家被害 51,337 棟(44 都道府県) と報告されている 1) 。また、停電約 8 万戸、総断水戸数 263,593 戸、 交通については、鉄道が 32 事業者 115 路線で運休停止となり、高速 道路も最大 17 路線 19 区間が通行止めになる等、ライフラインにつ いても各地で甚大な被害がもたらされた 1) 。特に岡山県では、真備 町における河川氾濫により大きな被害が生じ、また広島県では、広 島市や坂町、呉市、三原市等において同時多発的に発生した土砂災 害により多くの被害がもたらされた。愛媛県では河川氾濫や土砂災 害による被害に加えて、浄水場が土砂により壊滅的な被害を受ける 等、その被害の様相は地域によって多様であった 1) 。このような状 況から、これら三県では各地に災害ボランティアセンター(以下、 災害 VC)が立ち上げられた。災害 VC とは、被災住民のニーズの 把握・整理や支援活動を希望する個人や団体の受け入れ、両者のマ ッチングを行い、円滑かつ効率的なボランティア活動を推進するた めの組織で、被災地の早期復旧・復興に重要な役割を果たす。本稿 では、 平成 30 年 7 月豪雨の被災地である広島県三原市の災害 VC に て、筆者らが災害直後から直接スタッフとして入り、現場で実施し た GIS による情報支援活動(GIS 活用型情報支援活動)について報 告する。 地図を利活用した空間的な被害状況の把握は災害対応の基本であ り、2011 年の東日本大震災を受けて改正された災害対策基本法では、 地理空間情報の活用(第 51 条 2 項関係)および災害に関する情報の 共有(第 51 条 3 項関係)が努力義務として規定され、GIS を活用し た効果的な災害対応の実現が目標として挙げられている。このよう な状況の中、近年では、災害 VC における GIS を活用した災害対応 のための情報支援事例が報告されており 2)3)4)5) 、 その中でも述べられ ているように、GIS による効果的な災害対応手法提案のためには、 被災地における GIS 活用の実践事例等の知見の蓄積が必要と考えら れる。そこで本稿では、筆者らが三原市災害 VC にて実施した GIS 活用型情報支援活動について報告する。 2.対象地の被害と災害 VC の概要 2.1 対象地と被害概況 対象地である三原市は広島県南部に位置する、人口 96,194 人(平 成 27 年国勢調査)の地方都市である(図 1) 。南北に 2 級河川の沼 田川が流れており、以前より流域で洪水被害が発生してきた。実際 に、枕崎台風や昭和 42 年 7 月豪雨、6.29 豪雨災害の際にも、流域 *1 広島大学大学院工学研究科 博士課程後期・修士(工学) 日本学術振興会特別研究員(DC1) (〒739-8527 広島県東広島市鏡山 1-4-1) *1 Graduate Student, Graduate School of Engineering, Hiroshima Univ. Research Fellow of Japan Society for the Promotion of Science (DC1) *2 広島大学大学院工学研究科 博士課程前期 *2 Graduate Student, Graduate School of Engineering, Hiroshima Univ. *3 広島大学工学部 学生 *3 Student, Faculty of Engineering, Hiroshima University *4 広島大学大学院工学研究科 教授・博士(工学) *4 Professor, Hiroshima University, Ph.D *1 *2 *2 *2 *2 *3 *3 *1 *2 *2 *2 *3 *3 *4
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