Modulation of cytokine production by plant sterols in stimulated human Jurkat T cells.
The plant sterols campesterol, beta-sitosterol and beta-sitostanol were investigated for potential immunomodulatory effects in Jurkat T cells. Treatments involved supplementing cells with or without concanavalin A (ConA) or phorbol-12-myristate-13-acetate plus ionomycin (PMA+IoM) in the presence or absence of increasing concentrations (10-100 microM) of each plant sterol for 24 h. None of the plant sterols significantly affected mitogen-stimulated IL-4, IL-10 or IFN-gamma production. However, campesterol, beta-sitosterol and beta-sitostanol significantly suppressed mitogen-induced IL-2 production in a dose-dependent manner. Both bisindolylmaleimide-I (BIM-I), a specific protein kinase C (PKC) inhibitor, and the immunosuppressant drug known as Tacrolimus (FK506), an IL-2 inhibitor, prevented mitogen-stimulated IL-2 production in Jurkat cells. Treatment with PMA+IoM alone significantly increased PKC activity and the presence of BIM-I prevented PKC activation by PMA+IoM. Following 24 h treatments, the plant sterols did not affect PMA+IoM-enhanced PKC activity, cellular calcium content or calcineurin activity. Intracellular cyclic 3',5'-adenosine monophosphate (cAMP) levels were significantly reduced by PMA+IoM. The presence of FK506 prevented a PMA+IoM-induced reduction of intracellular cAMP. Likewise the plant sterols behaved in a similar manner as FK506. Our findings suggest that the suppression of IL-2 by the plant sterols was not mediated via PKC inhibition and that their effects occurred possibly via cAMP modulation and/or a calcium/calcineurin-independent pathway.
Aherne
S Aisling
SA
Department of Food and Nutritional Sciences, University College Cork, Cork, Republic of Ireland. a.aherne@ucc.ie
O'Brien
Nora M
NM
D002455:Cell Division; D002470:Cell Survival; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008301:Maleimides / Q000494:pharmacology; D010840:Phytosterols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012855:Sitosterols / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D007211:Indoles; D007376:Interleukin-2; D008301:Maleimides; D010840:Phytosterols; D012855:Sitosterols; D003208:Concanavalin A; C021273:campesterol; C025473:gamma-sitosterol; D002784:Cholesterol; C021255:stigmastanol; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus