Different Effects of Bortezomib on the Expressions of Various Protein Kinase C Isoenzymes in T Cells of Patients with Systemic Lupus Erythematosus and in Jurkat Cells

• Published in: Scandinavian journal of immunology Vol. 75; no. 2; pp. 243 - 248
• Main Authors: Griger, Z., Tóth, B. I., Baráth, S., Gyetvai, Á., Kovács, I., Tarr, T., Bíró, T., Zeher, M., Sipka, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012
• Subjects: Adult; Apoptosis; Apoptosis - drug effects; Boronic Acids - pharmacology; Bortezomib; Case-Control Studies; Cell proliferation; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Female; Gene Expression - drug effects; Humans; Isoenzymes; Isoenzymes - genetics; Isoenzymes - immunology; Jurkat Cells; Limiting factors; Lupus Erythematosus, Systemic - enzymology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocytes T; Male; Middle Aged; Organ Specificity; Primary Cell Culture; Proteasome Inhibitors - pharmacology; proteasomes; Protein kinase C; Protein Kinase C - genetics; Protein Kinase C - immunology; Protein Kinase C-delta - genetics; Protein Kinase C-delta - immunology; Protein Kinase C-epsilon - genetics; Protein Kinase C-epsilon - immunology; Protein Kinase C-theta; Pyrazines - pharmacology; Systemic lupus erythematosus; T-Lymphocytes - drug effects; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; T-Lymphocytes - pathology
• ISSN: 0300-9475; 1365-3083; 1365-3083
• DOI: 10.1111/j.1365-3083.2011.02647.x

The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 h 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 nine 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.