Abstract

Cyclosporine-A (CsA) is a widely used immunosuppressant. In this study, we explore the pathway through which CsA suppressed the Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced increase in matrix metalloproteinase (MMP) activities in co-cultured human gingival fibroblasts (HGFs) and THP-1 monocytes. In the co-culture, we found that CsA inhibited the expression of cyclophilin A (CyPA), CD147 and the activities of MMPs, which were all induced by P.g-LPS. We also found that P.g-LPS and recombinant human CyPA increased activation of ERK1/2 and IκB (an NF-κB inhibitory protein), but CsA and the anti-CD147 antibody significantly inhibited these effects. Taken together, CsA in the presence of P.g-LPS might suppress MMP activities by blocking the CyPA/CD147 interaction that results in the inhibition of ERK1/2 and NF-κB signaling by interfering with the phosphorylation of ERK1/2 and IκB.

摘要

环孢菌素-A (CsA) 是一种广泛使用的免疫抑制剂。在这项研究中，我们探索了 CsA 抑制牙龈卟啉单胞菌的途径在共培养的人牙龈成纤维细胞 (HGF) 和 THP-1 单核细胞中，脂多糖 (Pg-LPS) 诱导基质金属蛋白酶 (MMP) 活性增加。在共培养中，我们发现CsA抑制亲环蛋白A（CyPA）、CD147的表达和MMPs的活性，这些都是由Pg-LPS诱导的。我们还发现 Pg-LPS 和重组人 CyPA 增加了 ERK1/2 和 IκB（一种 NF-κB 抑制蛋白）的激活，但 CsA 和抗 CD147 抗体显着抑制了这些作用。总之，CsA 在 Pg-LPS 存在下可能通过阻断 CyPA/CD147 相互作用来抑制 MMP 活性，该相互作用通过干扰 ERK1/2 和 IκB 的磷酸化导致抑制 ERK1/2 和 NF-κB 信号传导。