title: Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury.
abstract: Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-α, IL-1β and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS.
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Izushi
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Teshigawara
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Dengli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wake
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Department of Pharmacology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Hideo Kohka
authors.initials: HK
authors.lastname: Takahashi
authors.affiliation: School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: mbori@md.okayama-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D056809:Alveolar Epithelial Cells; D000818:Animals; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D012995:Solubility
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products
keywords: AECI; ARDS; Anti-inflammation; LPS; RAGE