Anti‑inflammatory effect of salusin‑β knockdown on LPS‑activated alveolar macrophages via NF‑κB inhibition and HO‑1 activation

Chen,Sheng; Hu,Yunnan; Zhang,Jiaxin; Zhang,Pengyu

doi:10.3892/mmr.2020.11766

Anti‑inflammatory effect of salusin‑β knockdown on LPS‑activated alveolar macrophages via NF‑κB inhibition and HO‑1 activation

Authors:
- Sheng Chen
- Yunnan Hu
- Jiaxin Zhang
- Pengyu Zhang
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Affiliations: Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Emergency, Jilin Central General Hospital, Jilin, Jilin 132011, P.R. China
Published online on: December 8, 2020 https://doi.org/10.3892/mmr.2020.11766
Article Number: 127
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammation of alveolar macrophages is the primary pathological factor leading to acute lung injury (ALI), and NF‑κB activation and HO‑1 inhibition are widely involved in inflammation. Salusin‑β has been reported to contribute to the progression of the inflammatory response, but whether salusin‑β could regulate inflammation in lipopolysaccharide (LPS)‑induced ALI remains unknown. The present study aimed to investigate the role of salusin‑β in LPS‑induced ALI and to uncover the potential underlying mechanisms. Sprague‑Dawley rats were subjected to LPS administration, and then pathological manifestations of lung tissues, inflammatory cytokines levels in bronchoalveolar lavage fluid (BALF) and expression of salusin‑β in macrophages of lung tissues were assessed. NR8383 cells with or without salusin‑β knockdown were treated with LPS, and then the concentration of inflammatory cytokines, and the expression of high mobility group box‑1 (HMGB1), NF‑κB signaling molecules and heme oxygenase‑1 (HO‑1) levels were detected. The results showed that LPS caused injury of lung tissues, increased the levels of proinflammatory cytokines in BALF, and led to higher expression of salusin‑β or macrophages in lung tissues of rats. In vitro experiments, LPS also upregulated salusin‑β expression in NR8383 cells. Knockdown of salusin‑β using short hairpin (sh)RNA inhibited the LPS‑induced generation of inflammatory cytokines. LPS also enhanced HMGB1, phosphorylated (p)‑IκB and p‑p65 expression, but reduced HO‑1 expression in both lung tissues and NR8383 cells, which were instead inhibited by the transfection of sh‑salusin‑β. In addition, knockdown of HO‑1 using shRNA reversed the inhibitory effect of sh‑salusin‑β on the LPS‑induced generation of inflammatory cytokines, activation of NF‑κB signaling and inactivation of HO‑1. In conclusion, this study suggested that knockdown of salusin‑β may inhibit LPS‑induced inflammation in alveolar macrophages by blocking NF‑κB signaling and upregulating HO‑1 expression.

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