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ID 31812
JaLCDOI
フルテキストURL
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著者
Liu, Rui Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mori, Shuji Shujitsu University, School of Pharmacy
Wake, Hidenori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Zhang, Jiyong Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Liu, Keyue Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Izushi, Yasuhisa Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takahashi, Hideo K. Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Peng, Bo Shanghai University of Traditional Chinese Medicine
Nishibori, Masahiro Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
抄録

Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.

キーワード
RAGE
HMGB1
S100A12
heparin
inflammation
Amo Type
Original Article
発行日
2009-08
出版物タイトル
Acta Medica Okayama
63巻
4号
出版者
Okayama University Medical School
開始ページ
203
終了ページ
211
ISSN
0386-300X
NCID
AA00508441
資料タイプ
学術雑誌論文
言語
English
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Sience KeyUT