Different effects of Bortezomib on the expressions of various PKC isoenzymes in T cells of patients with systemic lupus erythematosus and in Jurkat cells
Griger, Z × Tóth, Balázs István Baráth, S Gyetvai, A Kovács, I Tarr, T Bíró, T Zeher, M Sipka, S #
Scandinavian Journal of Immunology vol:75 issue:2 pages:243-248
The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 hours on the protein kinase C (PKC) profiles, rates of proliferation and apoptosis in Jurkat cells and lymphocytes of 10 patients with systemic lupus erythematosus (SLE) and 9 healthy subjects. The expressions of PKC proteins, the rates of proliferation and apoptosis were determined. The effects of BZ were different in the Jurkat and lupus T cells. Whereas BZ elevated the expression of PKC θ, δ and ξ isoenzymes in the Jurkat cells, it was unable to do that in the lupus T cells. BZ induced a dose-dependent increase in the apoptosis of Jurkat cells, while decreased the proliferation. The same effect of BZ was observed on the apoptosis of lymphocytes both in SLE and healthy subjects at concentrations higher than the therapeutic dose. We conclude that BZ treatment in vitro was not able to restore the SLE specific defect (decrease) in the expression of PKC isoenzymes in the T cells as it was expected. This can be a limiting factor in the positive clinical effects of BZ in lupus. Keywords: apoptosis; bortezomib; human lymphocytes; Jurkat cells; protein kinase C (PKC); systemic lupus erythematosus (SLE).