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

Z. Griger, B. I. Tóth, S. Baráth, Á Gyetvai, I. Kovács, T. Tarr, T. Bíró, M. Zeher, S. Sipka

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Abstract

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

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalScandinavian Journal of Immunology
Volume75
Issue number2
DOIs
Publication statusPublished - 2012

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Jurkat Cells
Systemic Lupus Erythematosus
Protein Kinase C
Isoenzymes
T-Lymphocytes
Apoptosis
Healthy Volunteers
Lymphocytes
Bortezomib
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

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title = "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",
abstract = "The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24h 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.",
author = "Z. Griger and T{\'o}th, {B. I.} and S. Bar{\'a}th and {\'A} Gyetvai and I. Kov{\'a}cs and T. Tarr and T. B{\'i}r{\'o} and M. Zeher and S. Sipka",
year = "2012",
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TY - JOUR

T1 - 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

AU - Griger, Z.

AU - Tóth, B. I.

AU - Baráth, S.

AU - Gyetvai, Á

AU - Kovács, I.

AU - Tarr, T.

AU - Bíró, T.

AU - Zeher, M.

AU - Sipka, S.

PY - 2012

Y1 - 2012

N2 - The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24h 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.

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

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