Lactic Acid Inhibits the Cytotoxicity of NK-92 Cells via Activating the Lactate Receptor GPR81

Aims: Lactate acid functions as not only an energy source but a signaling molecule through the lactate receptor GPR81 under physiological conditions. However, pathological role of lactic in tumor microenvironment remains unclear, particularly for immune cells.
 Methodology: NK-92 cells were treated with L-lactic solutions at final concentrations 10, 20, 30, and 40 mM, its cell viability cytotoxicity on A549 A375 evaluated by CCK8 assay crystal violet assay, respectively. Furthermore, qPCR was used to assess expression cytotoxicity-related genes antagonist agonist. And their relationship between lactate/GPR81 pathway analyzed Pearson’s correlation.
 Results: The inhibited increasing concentration. Additionally, cytotoxic activity against decreased Moreover, results demonstrated that can be activated or agonist (3,5-DHBA) downregulate which included FASLG gene(Fas Ligand),TNF-α gene(Tumor necrosis factor-α), INFG gene (Interferon-γ), RPF1 (Perforin 1), GZMA (Granzyme A), GZMB B), GZMH H), GAMK K) GZMM M). returned near-control level when presence (3-OBA), did well. correlation analysis revealed coefficient seems negative.
 Conclusion: Lactic activate genes, subsequently lower cells.