The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. But, changes in the metabolism of normal synovial membranes or synovial cells during the early stages of inflammation remains unknown. Moreover, there are still many aspects of inflammatory signaling pathways altered by glycolysis inhibitors, that remain unclear. In this study we found that, in normal, non-pathological bovine synovial cells, most of ATP synthesis was generated by mitochondrial respiration. However, during the early of stages inflammation, initiated by lipopolysaccharide (LPS) exposure, synovial cells shifted to glycolysis for ATP production. The glycolysis inhibitor 2-deoxyglucose (2DG) reversed LPS induced increases in glycolysis for ATP production and suppressed the expression of inflammatory cytokines and proteolytic enzymes. 2DG suppressed the phosphorylation of the transcription factor cAMP response element binding protein (CREB) enhanced by LPS. Treatment with a CREB inhibitor reversed the expression of LPS-stimulated inflammatory cytokines and proteolytic enzymes. This study showed that changes in metabolism occur during the early stages of inflammation of synovial cells and can be reversed by 2DG and signaling pathways associated with CREB phosphorylation.

代谢重编程的参与被认为有助于类风湿性关节炎（RA）的病理生理学。 RA 患者滑膜细胞代谢中的糖酵解增强。已知糖酵解抑制剂具有抗炎作用。但是，炎症早期阶段正常滑膜或滑膜细胞的代谢变化仍然未知。此外，糖酵解抑制剂改变炎症信号通路的许多方面仍不清楚。在这项研究中，我们发现，在正常的、非病理性的牛滑膜细胞中，大部分 ATP 合成是由线粒体呼吸产生的。然而，在炎症的早期阶段，由于脂多糖 (LPS) 暴露引发，滑膜细胞转向糖酵解以产生 ATP。糖酵解抑制剂 2-脱氧葡萄糖 (2DG) 可逆转 LPS 诱导的 ATP 生成糖酵解增加，并抑制炎症细胞因子和蛋白水解酶的表达。 2DG 抑制 LPS 增强的转录因子 cAMP 反应元件结合蛋白 (CREB) 的磷酸化。 CREB ​​抑制剂治疗逆转了 LPS 刺激的炎症细胞因子和蛋白水解酶的表达。这项研究表明，代谢的变化发生在滑膜细胞炎症的早期阶段，并且可以通过 2DG 和与 CREB ​​磷酸化相关的信号通路逆转。