Abstract
Objective Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action. Methods The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. In vitro, ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome. Results The mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells. Conclusions LBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.
Highlights
Sepsis leads to multiple organ dysfunctions that can produce diverse critical illness [1]
To explore the effect of limb bud and heart (LBH) on acute lung injury (ALI) in vitro, we performed the LPS induction to produce LPS-induced ALI in A549 cells. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) exhibited that the LBH expression was inhibited or enhanced by the transfection of sh-LBH oroe-LBH into LPS-induced A549 cells (P < 0:001, Figure 2(a))
Our results showed that MCC950 effectively reversed the promoting effects of LBH silencing on the expression of IL-1β, IL-6, and IL-18 in the LPS-induced
Summary
Sepsis leads to multiple organ dysfunctions that can produce diverse critical illness [1]. Lung dysfunction, referred to as acute lung injury (ALI), is generally associated with sepsis [2]. ALI is characterized by pulmonary alveoli edema, mitochondrial dysfunction, and exuberant proinflammatory responses [3]. More than 40% of ALI patients have disseminated intravascular coagulation or hematological, cardiovascular, and neurological dysfunctions; all of which were related to higher mortality [4]. The antiinflammatory drugs for ALI are inefficient, and the treatments of ALI require high costs [5, 6]. It is essential to explore new approaches for the treatment of ALI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
