Nesfatin-1 alleviated lipopolysaccharide-induced acute lung injury through regulating inflammatory response associated with macrophages modulation

Abstract

AbstractAcute lung injury (ALI) is a continuum of lung changes associated with uncontrolled excessive lung inflammation. However, the pathogenesis of ALI is still complicated and effective clinical pharmacological management is required. Various signaling pathways are involved in the inflammatory responses of ALI. Here, we aimed to explore the role of nesfatin-1, an amino-acid peptide with anti-inflammatory action, in an LPS-induced ALI mice model, and its role in regulating macrophages in response to LPS stimulation in vitro. This was to clarify the underlying mechanisms of regulating the inflammatory response in the development of ALI. The results show that nesfatin-1 expression was downregulated in the lung tissues of ALI mice compared to control mice. Nesfatin-1 treatment ameliorated the inflammatory response and lung tissue damage in LPS-induced ALI in mice. In vitro studies showed that nesfatin-1 attenuated the generation and release of proinflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in LPS-induced RAW 264.7 cells. Nesfatin-1 also inhibited reactive oxygen species production and improved superoxide dismutase (SOD) activity in LPS-induced RAW 264.7 cells. These findings suggest that nesfatin-1 exerted a crucial role in regulating the LPS-mediated activation of M1 macrophages. Further mechanism investigations indicated that nesfatin-1 inhibited the activation of p38 MAPK/c-Jun and NF-κB pathways in LPS-induced RAW 264.7 cells, as evidenced by decreased expression levels of p-p38, p-c-Fos, and p-p65. Overall, nesfatin-1 alleviated LPS-induced ALI, which might be attributed to regulating inflammatory response through macrophages modulation.