Effect of cathepsin inhibitors in signals associated with Th1 and Th2 mediators by Dendritic Cells. Mus musculus

Cathepsin inhibitors have been associated to induce changes in Th1/Th2 polarization; cathepsin B inhibitor CA074 has been reported to induce a Th1 polarization, whereas cathepsin L inhibitor CLIK148 has been reported to induce a Th2 polarization. In this study, we pre-treated bone marrow-derived dendritic cells (BMDC) with CA074Me or CLIK148, followed by stimulation with a known pro-Th1 inducer (CpG) and a known pro-Th2 inducer (TNF-alpha) and analyzed by microarrays the expression of genes acting as pro-Th1 or pro-Th2 mediators. Overall design: A total of 7 experimental conditions were used, and the experiments were performed independently twice; thus, a total of 14 samples were analyzed. We included the following controls: BMDC treated with only DMSO (solvent control) with no stimulation, BMDC pre-treated with either CA074Me or CLIK148 without any stimulation, and BMDC pre-treated with DMSO and further stimulated with either CpG or TNF-alpha.