Interleukin-6 stimulates cathepsin B and L activities of human periodontal ligament cells through the signaling pathways

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Our in vitro study examined the secretion of cathepsin B(CAB) and cathepsin L(CAL) in PDL cells following mechanical stress. PDL cells were subjected to 0.5, 1.0, 2.0, or 3.0 g/cm^2 of compression force or an increase in surface area by tension force of 0.28%, 0.95%, 1.72%, or 2.50% for 24 hr. We found compression and tension significantly increased the secretions of both CAB and CAL in PDL cells, which were exhibited in a time- and force magnitude-dependent manner. The compression-stimulated secretion of CAB was increased approximately 3-fold and that of CAL 4-fold, as compared with the control. Further, tension-stimulated secretion of CAB was increased by 1.5-fold and that of CAL 2-fold compared with the control. When analyzed using a semiquantitative polymerase chain reaction(RT-PCR) assay, CAB and CAL mRNA were increased in response to both compression and tension forces. These findings demonstrated that mechanical stress (compression and tension forces) causes an increase in secretion of CAB and CAL in PDL cells in vitro.Furthermore, we examined that the mechanisms controlling CAB and CAL activities and intracellular signaling by IL-6 in orthodontic tooth movement. Cultured PDL cells were treated with different concentrations (0.01-10 ng/ml) of IL-6 in the absence or presence of the p38 MAP kinase inhibitor SB-208350 or the p42/44 inhibitor PD-98059. Protein and gene expression of CAB and CAL were determined by ELISA and PCR, respectively. SB-208350 and PD-98059 inhibited the increase in CAB and CAL production induced by IL-6. These results suggest the IL-6 regulates muscle CAB and CAL production at least in part by activating the MAP kinase pathway and NF-kappaB.