Differential effects of lactacystin on cytokine production in activated Jurkat cells and murine splenocytes.
Previous studies have demonstrated that the proteasome inhibitor, lactacystin, suppresses cytokine production and induction of other inflammatory mediators by LPS-stimulated macrophages. The purpose of the present studies was to determine the effect of lactacystin upon the function of activated human Jurkat T cells and murine splenocytes. Lactacystin treatment suppressed interleukin (IL)-2, interferon (IFN)gamma, and IL-13 production similarly in both activated Jurkat cells and primary splenocytes. Interestingly, lactacystin produced differential effects on IL-4 transcription in the two models. While lactacystin inhibited IL-4 mRNA transcription in primary splenocytes, it induced IL-4 mRNA in a concentration-dependent manner in Jurkat cells. The increase in IL-4 mRNA levels by lactacystin did not correlate with increases in T(H2)-specific transcription factors, avian musculoaponeurotic fibrosarcoma AS42 oncogene homolog (c-maf) or GATA binding protein 3 (GATA-3). In addition, the binding of both GATA-3 and t-bet to their respective response elements was essentially unchanged by lactacystin treatment in both splenocytes and Jurkat T cells, suggesting the induction of IL-4 is due to other mechanisms. Collectively, the current studies suggest proteasomal activity has differential effects on IL-4 transcription in activated Jurkat cells and primary splenocytes.
Rockwell
Cheryl E
CE
Department of Basic Medical Science, School of Medicine, and Shock/Trauma Research Center, University of Missouri Kansas City, Kansas City, MO 64108, USA. crockwell@kumc.edu
Qureshi
Nilofer
N
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000187:drug effects; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D000098815:T-bet Transcription Factor
D016207:Cytokines; D050990:GATA3 Transcription Factor; D061988:Proteasome Inhibitors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C067713:lactacystin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine