RBM3 is associated with acute lung injury in septic mice and patients via NF- κB/NLRP3 pathway

Abstract

Abstract Sepsis refers to host response disorders caused by infection, which can lead to life-threatening organ dysfunction. And the lungs bear the brunt of the disease. RNA-binding motif protein 3 (RBM3) is an important cold-shock protein that is upregulated in response to mild hypothermia or hypoxia. In this study, we aimed to investigate whether RBM3 is involved in sepsis-associated acute lung injury (ALI). Intraperitoneal injection of LPS (10 mg/kg) was performed in wild-type (WT) and RBM3 knockout (KO, RBM3-/-) mice to establish an in vivo sepsis model. An NLRP3 inflammasome inhibitor, MCC950 (50 mg/kg), was injected intraperitoneally 30 min before LPS treatment, and serum, lung tissues, and BALF were collected 24 h later for further analysis. In addition, we also collected serum from sepsis patients and healthy volunteers to detect RBM3 expression. The results showed that the expression of RBM3 in the lung tissues of LPS-induced sepsis mice and the serum of patients with sepsis was significantly increased and positively correlated with disease severity. In addition, RBM3 knockout (KO) mice had a low survival rate, and RBM3 KO mice had more severe lung damage, inflammation, lung cell apoptosis, and oxidative stress than WT mice. After the LPS treatment, the levels of nucleotide binding and oligomerization domain-like receptor family 3 (NLRP3) inflammasomes and mononuclear cell nuclear factor-κB (NF-κB) in the lung tissues of RBM3 KO mice were significantly higher. However, they were only slightly elevated in WT mice. Interestingly, MCC950 improved LPS-induced acute lung injury in WT mice and RBM3 KO mice, and inhibited the expression of NLRP3, caspase-1, and IL-1β. In conclusion, RBM3 was overexpressed in sepsis patients and LPS-induced mice. The RBM3 gene deficiency aggravated sepsis-associated ALI through the NF-κB/NLRP3 pathway.