title: Acteoside attenuates TSLP-induced mast cell proliferation via down-regulating MDM2.
abstract: Acteoside (verbascoside) is extensively distributed in Abeliophyllum distichum and has antimicrobial and anti-inflammatory properties. Thymic stromal lymphopoietin (TSLP) has a pivotal function in the pathogeneses of inflammatory diseases through increasing the mast cell proliferation via the activation of murine double minute 2 (MDM2). Here, we investigate whether acteoside attenuates the MDM2 expression in a TSLP-stimulated human mast cell line (HMC-1 cells). In these cells, TSLP induced the up-regulation of MDM2 and the down-regulation of p53; however, in the TSLP-stimulated HMC-1 cells, the acteoside down-regulated the MDM2 and up-regulated the p53. Increases in the phosphorylation of the single transducer and activation of transcription 6 and 5 via TSLP are decreased by acteoside. The interleukin (IL)-13 (a mast cell growth factor), IL-6, tumor necrosis factor-α, and IL-1β levels are significantly reduced by the acteoside in the TSLP-stimulated HMC-1 cells, and the acteoside significantly induces the activation of caspase-3, the cleavage of poly-ADP-ribose polymerase, and the reduction of the procaspase-3 and Bcl2. Furthermore, the mRNA expressions of the TSLP receptor and IL-7 receptor that increase due to TSLP are reduced by the acteoside. In conclusion, these results indicate that acteoside is a specific regulator of MDM2 activation in TSLP-stimulated mast cells, which indicates its potential use for the treatment of mast cell-mediated inflammatory diseases.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Myoung-Schook
authors.initials: MS
authors.lastname: Yoou
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea. Electronic address: hmkim@khu.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D015536:Down-Regulation; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000094632:Thymic Stromal Lymphopoietin; D059808:Polyphenols
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005960:Glucosides; D010636:Phenols; D051736:Proto-Oncogene Proteins c-mdm2; D000094632:Thymic Stromal Lymphopoietin; C058956:acteoside; D059808:Polyphenols; C497206:MDM2 protein, human
keywords: Acteoside; Caspase-3; Interleukin-13; Murine double minute 2; Signal transducer and activator of transcription 6; p53