title: Differential effects of lactacystin on cytokine production in activated Jurkat cells and murine splenocytes.
abstract: 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.
authors.affiliation: 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
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Rockwell
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
mesh_terms: 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
chemical_list: 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