LT-α Facilitates the Aerobic Glycolysis and M1 Polarization of Macrophages by Activating the NF-κB Signaling Pathway in Intervertebral Disc Degeneration

Chensheng Qiu,1– 3 Zhu Guo,4 Junhua Yuan,5 Hongfei Xiang,4 Bohua Chen,4 Yuanxue Yi,2 Yongsheng Zhao1 1Department of Spinal Surgery, Qingdao Municipal Hospital, Qingdao, 266011, People’s Republic of China; 2Department of Laboratory Medicine, Chongqing Precision Medical Industry Technology Research Institute, Chongqing, 400000, People’s Republic of China; 3Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Spinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 5Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, 266021, People’s Republic of ChinaCorrespondence: Yongsheng Zhao; Yuanxue Yi, Email [email protected]; [email protected]: Injury and inflammatory activate and polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried to explore the mechanisms that regulate macrophage polarization, providing new insights and targets for IVDD treatment. The aim of our study was to evaluate the influence of LT-α on aerobic glycolysis (AG) and polarization in macrophages.Methods: M0 macrophages were achieved by stimulating THP-1 cells with PMA. M1 macrophages were obtained by IFN-γ and LPS stimulation in M0 macrophages. Energy metabolomics, AG and apoptosis related protein expression, migration and invasion measurement, proliferation was analyzed. Polarization of macrophages, AG associated genes expression, macrophage recruitment was evaluated. NF-κB signaling was ascertained by laser confocal and Western blotting.Results: The propanoate metabolism pathway was enriched in LT-α overexpressing M0 macrophages, and various energy metabolites were detected. Glucose absorption, lactic acid production, and levels of AG proteins were strikingly increased in LT-α overexpression macrophages and remarkably repressed in LT-α knockdown macrophages, accompanied by activated and inactivated NF-κB signaling, respectively. Suppressed migration and invasion ability, restrained proliferation, activated AG, and enhanced apoptosis were observed in nucleus pulposus (NP) cells treated by LT-α overexpressed macrophages, accompanied by reduced macrophage recruitment, with opposite results when treated by LT-α knockdown macrophages. The enhanced M1 polarization and activated AG in LT-α overexpression macrophages were abolished by co-culturing with NF-κB inhibitor.Conclusion: LT-α facilitates the AG and M1 polarization of macrophages via activating the NF-κB signaling pathway.Keywords: LT-α, macrophage polarization, aerobic glycolysis, nucleus pulposus cells, NF-κB signaling pathway