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

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.