Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade

Kenjiro Ishii, Hiroya Takeuchi, Koichi Fukunaga, Yuki Hirano, Koichi Suda, Tomoko Hagiwara, Taku Miyasho, Shingo Yamada, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hirofumi Kawakubo, Yoshirou Saikawa, Tai Omori, Tomoko Betsuyaku, Atsuhiro Ichihara, Yuko Kitagawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose/Aim: We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. Materials: We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d). Methods: We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung. Results: The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorrhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin. Conclusions: The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalExperimental Lung Research
Volume41
Issue number4
DOIs
Publication statusPublished - 2015 May 1

Keywords

  • (pro)renin receptor blocker
  • Acute lung injury
  • Prorenin
  • Reninangiotensin system

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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  • Cite this

    Ishii, K., Takeuchi, H., Fukunaga, K., Hirano, Y., Suda, K., Hagiwara, T., Miyasho, T., Yamada, S., Nakamura, R., Takahashi, T., Wada, N., Kawakubo, H., Saikawa, Y., Omori, T., Betsuyaku, T., Ichihara, A., & Kitagawa, Y. (2015). Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade. Experimental Lung Research, 41(4), 199-207. https://doi.org/10.3109/01902148.2014.993444