title: Effect of thymoquinone on mouse dendritic cells.
abstract: Thymoquinone, a component of Nigella sativa is known to confer protection against tumour growth due to stimulation of tumour cell apoptosis. Moreover, thymoquinone has remarkable anti-inflammatory potency. Surprisingly, despite its powerful influence on inflammation and its immunomodulatory effects, little is known about its effect on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. DC maturation and cytokine release is triggered by bacterial components such as lipopolysaccharides (LPS). The present study explored whether thymoquinone modifies LPS-induced DC maturation, survival and cytokine release. To this end, mouse bone marrow derived DCs were treated with LPS and different concentrations of thymoquinone and the surface expression of CD11c, CD86, MHCII, CD54 and CD40 was determined by FACS analysis, the formation of the interleukins 10 (IL-10) and 12 (IL-12p70) as well as TNF-alpha by ELISA, caspase activation by FITC-labelled antibodies (FACS), cell membrane scrambling by annexin V binding (FACS) and Akt and ERK1/2 phosphorylation by Western blotting. LPS increased the percentage of CD11c(+)CD86(+), CD11c(+)MHCII(+), CD11c(+)CD40(+) and CD11c(+)CD54(+) cells and stimulated the release of IL-10, IL-12p70 and TNF-alpha. These effects were blunted by thymoquinone in a concentration dependent manner (1-20 microM). Moreover, LPS decreased and thymoquinone increased caspase 3 and caspase 8 activation and annexin V binding. Moreover, LPS-induced phosphorylation of prosurvival kinases Akt and ERK1/2 was abrogated by thymoquinone. In conclusion, thymoquinone compromises the maturation, cytokine release and survival of DCs.
authors.affiliation: Department of Physiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Xuan
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051940:B7-2 Antigen / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology*; D039521:CD11c Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000893:Anti-Inflammatory Agents; D051940:B7-2 Antigen; D016227:Benzoquinones; D039521:CD11c Antigen; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; C003466:thymoquinone