Tryptanthrin reduces mast cell proliferation promoted by TSLP through modulation of MDM2 and p53 - 02/04/16
, Hyun-Ja Jeong b, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
Background |
Atopic dermatitis (AD) results from complex interactions between mast cells and inflammatory mediators. An inflammatory mediator, thymic stromal lymphopoietin (TSLP) is known to promote mast cell proliferation through up-regulation of mouse double minute 2 (MDM2, a negative regulator of p53) and aggravate AD. In this study, we investigated whether tryptanthrin (TR, an anti-inflammatory agent) would regulate TSLP-induced mast cell proliferation and TSLP-induced a pro-inflammatory cytokine, tumor necrosis factor (TNF)-α production from mast cells.
Methods |
Human mast cell line (HMC-1) cells were treated with TR and stimulated with TSLP. Proliferation was measured with a bromodeoxyuridine incorporation assay. And pro- and anti-apoptotic factors were analyzed with quantitative real-time PCR, Western blot analysis, and ELISA. The mRNA expression and production of TNF-α were analyzed with quantitative real-time PCR and ELISA.
Results |
TR significantly inhibited the proliferation of HMC-1 cells promoted by TSLP. TR inhibited MDM2 expression, whereas TR increased the expression of p53, poly ADP-ribose polymerase, and caspase-3 in the TSLP-stimulated HMC-1 cells. TR significantly inhibited Ki67 mRNA expression as well as mRNA expression and production of interleukin (IL)-13 in the TSLP-stimulated HMC-1 cells. Moreover, TR significantly suppressed mRNA expression and production of TNF-α in the TSLP-stimulated HMC-1 cells. Finally, the mRNA expression of IL-7 receptor α chain and TSLP receptor was inhibited by TR in the TSLP-stimulated HMC-1 cells.
Conclusion |
Our results suggest that TR determined with new concept has intensive potential for the treatment of mast cell-mediated allergic diseases, such as AD.
Le texte complet de cet article est disponible en PDF.Abbreviations : AD, BrdU, FBS, HMC-1, IL, IMDM, MDM2, TR, TSLP
Keywords : Tryptanthrin, Thymic stromal lymphopoietin, Mouse double minute 2, Mast cells, Proliferation
Plan
Vol 79
P. 71-77 - avril 2016 Retour au numéro
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