TY - JOUR
T1 - Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade
AU - Ishii, Kenjiro
AU - Takeuchi, Hiroya
AU - Fukunaga, Koichi
AU - Hirano, Yuki
AU - Suda, Koichi
AU - Hagiwara, Tomoko
AU - Miyasho, Taku
AU - Yamada, Shingo
AU - Nakamura, Rieko
AU - Takahashi, Tsunehiro
AU - Wada, Norihito
AU - Kawakubo, Hirofumi
AU - Saikawa, Yoshiro
AU - Omori, Tai
AU - Betsuyaku, Tomoko
AU - Ichihara, Atsuhiro
AU - Kitagawa, Yuko
N1 - Publisher Copyright:
© 2015 Informa Healthcare USA, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
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U2 - 10.3109/01902148.2014.993444
DO - 10.3109/01902148.2014.993444
M3 - Article
C2 - 25844689
AN - SCOPUS:84928480404
SN - 0190-2148
VL - 41
SP - 199
EP - 207
JO - Experimental Lung Research
JF - Experimental Lung Research
IS - 4
ER -