Laminarin Alleviates Acute Lung Injury Induced by LPS Through Inhibition of M1 Macrophage Polarisation

Abstract

The lipopolysaccharide-induced acute lung injury (ALI) mouse model is used to simulate human acute respiratory distress syndrome (ARDS), which has a high mortality rate. An imbalance between M1 and M2 macrophages, characterised by an increase in M1 macrophages, was observed in sepsis-induced ALI. We report that laminarin, an active ingredient found in algae, exhibits exceptional performance in a mouse model of sepsis-induced ALI. It ameliorates lung edema, enhances the survival rate of mice and reduces the levels of the inflammatory factors TNF-α and IL-6. Furthermore, laminarin reduced the expression of CD86, which are markers associated with M1 macrophages. Laminarin treatment reduces the secretion of TNF-α and IL-6 in LPS-stimulated macrophages. Laminarin treatment also decreases glucose uptake in LPS-stimulated macrophages. Transcriptome sequencing reveals that genes downregulated in LPS-stimulated macrophages following laminarin treatment are predominantly enriched in the HIF-1α signalling pathway. Experimental validation confirms that laminarin treatment of LPS-stimulated macrophages reduces the expression of HIF-1α and significantly decreases the expression of related indicators ROS and NLRP3. After using siRNA to knock down HIF-1α in RAW264.7 cells, the inhibitory effect of laminarin on LPS-induced M1 polarisation of macrophages is abolished. This suggests that laminarin may potentially inhibit macrophage polarisation towards the M1 phenotype by downregulating the HIF-1α signal. In conclusion, the data presented in our study demonstrate that laminarin can effectively reduce M1 macrophage polarisation by downregulating HIF-1α signalling. This makes it a novel candidate drug for the treatment of LPS-induced ALI.