Apelin-13 Administration Protects Against LPS-Induced Acute Lung Injury by Inhibiting NF-κB Pathway and NLRP3 Inflammasome Activation

Abstract

Background/Aims: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS. Methods: The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining. Results: LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells. Conclusion: Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.

Dexmedetomidine alleviates blunt chest trauma and hemorrhagic shock‑resuscitation‑induced acute lung injury through inhibiting the NLRP3 inflammasome

“…These cytokines are released to induce selective recruitment of monocytes, neutrophils and lymphocytes, eventually causing pyroptosis, a novel form of programed cell death (34,35), which leads to tissue damage as a consequence. ali/ardS pathogenesis is closely associated with the NLRP3 inflammasome in lipopolysaccharide (lPS)-induced mouse and macrophage models (36), in lPS-induced animal models of ali (36,37), and in cecal ligation perforation (38). The present study demonstrated that nlrP3, aSc and caspase-1 expression levels were elevated in the ali group, which was consistent with the aforementioned studies.…”

Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans

“…Recently, GSK developed a recombinant human ACE2, GSK2586881 for treatment of acute respiratory distress syndrome (ARDS) and showed that this molecule was well-tolerated in clinical trials 49 . Corroborating on this, apelin signalling induces ACE2 expression in failing hearts 12 , and protects against lung injury in experimental models of acute respiratory distress syndrome 50 , possibly by inhibiting the NF-κB pathway and components of the inflammasome 51 . Furthermore, apelin counteracts the effects of angiotensin-II signalling, which is negatively regulated by ACE2, suggesting that targeting ACE2 and apelin could be a potentially novel therapeutic strategy for treatment of lung injury related pathologies and heart failure.…”

Apelin abrogates the stimulatory effects of 17β-estradiol and insulin-like growth factor-1 on proliferation of epithelial and granulosa ovarian cancer cell lines via crosstalk between APLNR and ERα/IGF1R

“…Apelin protects against apoptosis in cardiac tissues by regulating FoxO1 in mice [40] and by upregulating Bcl-2 and downregulating Bax together with cleaved caspase-3 in rats [41]. In addition, apelin alleviates oxidative stress and mitochondria-mediated apoptosis in mice [42]. Apelin induces expression of the antiapoptotic protein B cell lymphoma 2 and decreases production of the proapoptotic protein Bax in osteoblasts [43].…”