Lysophosphatidic acid regulates macrophage polarisation via LPAR1 by suppressing inflammatory responses and promoting M2-like characteristics

Abstract Introduction Lysophosphatidic acid (LPA) is a crucial bioactive lipid mediator involved in various physiological processes. However, its role in macrophage polarisation remains poorly understood. The aim of this study was to elucidate the modulatory effect of LPA on macrophage polarisation, particularly its ability to shift M1 macrophages toward an M2-like phenotype. Methods Using murine macrophage RAW264.7 cells, we confirmed the expression of LPA receptor 1 (LPAR1) through immunofluorescence staining. Results Treatment of resting M0 macrophages with LPA decreased inflammatory cytokines (IL-6, TNF-α) and increased TGF-β; similar effects were observed in LPS-stimulated cells and were reversed by the LPAR1 inhibitor AM095. Immunostaining demonstrated a notable shift from an M1- to M2-like phenotype, as evidenced by an increase in the arginase-1/CD68 ratio. Furthermore, LPA significantly decreased lactate production and increased ATP production in M1 macrophages. LPA promoted a shift toward oxidative phosphorylation in M1 macrophages, suggesting metabolic reprogramming toward an M2-like phenotype. Treatment with LPA significantly influenced macrophage polarisation, promoting a shift from a pro-inflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype. Conclusion These results suggest that treatment with LPA may help ameliorate diseases characterised by aberrant macrophage polarisation. Our study provides insights for the development of potential therapeutic strategies for inflammatory and autoimmune diseases.