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.