Curcumin differentially modulates mRNA profiles in Jurkat T and human peripheral blood mononuclear cells.
Curcumin, the yellow pigment of the rhizome of Curcuma longa is known to inhibit the transcription factors AP-1, Egr-1, NF-kappaB, c-myc and several important signaling kinases. We therefore investigated the differential effects of curcumin in concentation between 1.5 and 13.6 microM on gene expression in T Jurkat CD4(+) and human peripheral blood mononuclear cells (PBMCs). Relative quantification with reverse transcription real-time PCR (RT-rt-PCR) showed that low concentrations of curcumin significantly down-regulated mitogen-induced granulocyte macrophage colony stimulating factor (GM-CSF) mRNA (3- to 5-fold at 3 microM) in a dose- and time-dependent manner in both cell types. In comparison, the down-regulation of inducible nitric oxide (iNOS) mRNA levels was less pronounced, but interferon gamma (IFN-gamma) mRNA was dose-dependently up-regulated with curcumin concentrations up to 8.2 microM. Cyclin D1 mRNA expression was specifically inhibited in Jurkat T cells and stimulated PBMCs. The transcription factors NF-kappaB and NF-ATc were not affected in PBMCs. Interleukin-2 (IL-2), and-6 (IL-6) mRNAs levels were not influenced markedly by curcumin in stimulated PBMCs, but significantly reduced in stimulated Jurkat T cells. In addition, cytotoxic effects and down-regulation of mRNAs, including p65 and the house-keeping genes could only be measured in Jurkat T cells. These findings confirm previous reports on the anti-neoplastic potential of curcumin and show that this compound differentially modulates the expression profile of Th1 cells and PBMCs.
Gertsch
Jürg
J
Swiss Federal Institute of Technology Zurich, Institute of Pharmaceutical Sciences, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Güttinger
Martin
M
Heilmann
Jörg
J
Sticher
Otto
O
D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis
D016207:Cytokines; D017931:DNA Primers; D007376:Interleukin-2; D008934:Mitogens; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate