PMID- 20427199 OWN - NLM STAT- MEDLINE DCOM- 20100901 LR - 20211020 IS - 1096-0023 (Electronic) IS - 1043-4666 (Print) IS - 1043-4666 (Linking) VI - 51 IP - 1 DP - 2010 Jul TI - Differential effects of lactacystin on cytokine production in activated Jurkat cells and murine splenocytes. PG - 12-7 LID - 10.1016/j.cyto.2010.03.018 [doi] AB - 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. CI - Copyright 2010 Elsevier Ltd. All rights reserved. FAU - Rockwell, Cheryl E AU - Rockwell CE AD - 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 FAU - Qureshi, Nilofer AU - Qureshi N LA - eng GR - RR016475/RR/NCRR NIH HHS/United States GR - K99 ES018885/ES/NIEHS NIH HHS/United States GR - GM050870/GM/NIGMS NIH HHS/United States GR - R01 GM050870/GM/NIGMS NIH HHS/United States GR - R01 GM050870-17/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100427 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Cytokines) RN - 0 (GATA3 Transcription Factor) RN - 0 (Proteasome Inhibitors) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 133343-34-7 (lactacystin) RN - 9007-49-2 (DNA) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*analogs & derivatives/pharmacology MH - Animals MH - Cell Separation MH - Cytokines/*biosynthesis MH - DNA/metabolism MH - GATA3 Transcription Factor/metabolism MH - Humans MH - Jurkat Cells MH - Lymphocyte Activation/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Proteasome Inhibitors MH - Protein Binding/drug effects MH - Spleen/*cytology/*immunology MH - T-Box Domain Proteins/metabolism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Th2 Cells/drug effects/immunology PMC - PMC2911229 MID - NIHMS201594 EDAT- 2010/04/30 06:00 MHDA- 2010/09/02 06:00 PMCR- 2011/07/01 CRDT- 2010/04/30 06:00 PHST- 2009/04/09 00:00 [received] PHST- 2010/01/08 00:00 [revised] PHST- 2010/03/30 00:00 [accepted] PHST- 2010/04/30 06:00 [entrez] PHST- 2010/04/30 06:00 [pubmed] PHST- 2010/09/02 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - S1043-4666(10)00092-X [pii] AID - 10.1016/j.cyto.2010.03.018 [doi] PST - ppublish SO - Cytokine. 2010 Jul;51(1):12-7. doi: 10.1016/j.cyto.2010.03.018. Epub 2010 Apr 27.