PMID- 20110691 OWN - NLM STAT- MEDLINE DCOM- 20100408 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 25 IP - 2-3 DP - 2010 TI - Effect of thymoquinone on mouse dendritic cells. PG - 307-14 LID - 10.1159/000276563 [doi] AB - 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. CI - Copyright 2010 S. Karger AG, Basel. FAU - Xuan, Nguyen Thi AU - Xuan NT AD - Department of Physiology, University of Tubingen, 72076 Tubingen, Germany. FAU - Shumilina, Ekaterina AU - Shumilina E FAU - Qadri, Syed M AU - Qadri SM FAU - Gotz, Friedrich AU - Gotz F FAU - Lang, Florian AU - Lang F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100112 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Annexin A5) RN - 0 (Anti-Inflammatory Agents) RN - 0 (B7-2 Antigen) RN - 0 (Benzoquinones) RN - 0 (CD11c Antigen) RN - 0 (CD40 Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.4.22.- (Caspase 3) RN - O60IE26NUF (thymoquinone) SB - IM MH - Animals MH - Annexin A5/metabolism MH - Anti-Inflammatory Agents/*pharmacology MH - B7-2 Antigen/metabolism MH - Benzoquinones/*pharmacology MH - CD11c Antigen/metabolism MH - CD40 Antigens/metabolism MH - Caspase 3/metabolism MH - Dendritic Cells/*drug effects/immunology MH - Intercellular Adhesion Molecule-1/metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2010/01/30 06:00 MHDA- 2010/04/09 06:00 CRDT- 2010/01/30 06:00 PHST- 2009/10/27 00:00 [accepted] PHST- 2010/01/30 06:00 [entrez] PHST- 2010/01/30 06:00 [pubmed] PHST- 2010/04/09 06:00 [medline] AID - 000276563 [pii] AID - 10.1159/000276563 [doi] PST - ppublish SO - Cell Physiol Biochem. 2010;25(2-3):307-14. doi: 10.1159/000276563. Epub 2010 Jan 12.