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.
Keywords: CD147; Cyclosporin A; cyclophilin A; matrix metalloproteinases.