Role of soluble receptor for advanced glycation end products on endotoxin-induced lung injury

Haiying Zhang, Sadatomo Tasaka, Yoshiki Shiraishi, Koichi Fukunaga, Wakako Yamada, Hiroyuki Seki, Yuko Ogawa, Keisuke Miyamoto, Yasushi Nakano, Naoki Hasegawa, Taku Miyasho, Ikuro Maruyama, Akitoshi Ishizaka

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Rationale: The interaction of receptor for advanced glycation end products (RAGE) and its ligands often leads to inflammatory processes or tissue injury, although the effect of the blockade of RAGE signaling on lung injury remains to be investigated. Objectives: Using a murine model of lung injury induced by intratracheal lipopolysaccharide (LPS), we evaluated RAGE expression in the airspace and the effect of recombinant soluble RAGE (sRAGE) on LPS-induced lung injury. Methods: First, the expression of sRAGE in bronchoalveolar lavage (BAL) fluid was determined at 24 hours after intratracheal instillation of LPS or phosphate-buffered saline. Next, to evaluate the effect of sRAGE, BAL fluid was collected for cell counting and measurements of lung permeability and cytokine concentrations 24 hours after intratracheal LPS in the mice with or without intraperitoneal administration of sRAGE 1 hour after the instillation. In another series, lungs were sampled for histopathology and detection of apoptotic cells. The activation of nuclear factor (NF)-κB was analyzed 4 hours after LPS instillation. Measurements and Main Results: In response to LPS challenge, a RAGE isoform of 48 kD was detected in the BAL fluid. Treatment with sRAGE significantly attenuated the increases in neutrophil infiltration, lung permeability, production of inflammatory cytokines, NF-κB activation, and apoptotic cells in the lung as well as development of pathologic changes after LPS instillation. Conclusions: RAGE plays an important role in the pathogenesis of LPS-induced lung injury in mice. It was suggested that sRAGE should be tested as a treatment modality in other models of acute lung injury.

元の言語English
ページ(範囲)356-362
ページ数7
ジャーナルAmerican journal of respiratory and critical care medicine
178
発行部数4
DOI
出版物ステータスPublished - 2008 8 15

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Zhang, H., Tasaka, S., Shiraishi, Y., Fukunaga, K., Yamada, W., Seki, H., Ogawa, Y., Miyamoto, K., Nakano, Y., Hasegawa, N., Miyasho, T., Maruyama, I., & Ishizaka, A. (2008). Role of soluble receptor for advanced glycation end products on endotoxin-induced lung injury. American journal of respiratory and critical care medicine, 178(4), 356-362. https://doi.org/10.1164/rccm.200707-1069OC