title: Inhibition of MDM2 expression by rosmarinic acid in TSLP-stimulated mast cell.
abstract: Rosmarinic acid (RA) has an anti-inflammatory property while thymic stromal lymphopoietin (TSLP) has an important role in mast cell-mediated inflammatory responses. Thus, the aim of this study was to determine the regulatory effect of RA in TSLP-stimulated human mast cell line, HMC-1 cells, and short ragweed pollen-induced allergic conjunctivitis mouse model. As a result, we found that RA significantly decreased the TSLP-induced mast cell proliferation and murine double minute (MDM) 2 expression. RA significantly decreased the levels of interleukin (IL)-13 and phosphorylated the signal transducer and activation of transcription 6 in the TSLP-stimulated HMC-1 cells. RA induced the increment of p53 levels, caspase-3 activation, and poly-ADP-ribose polymerase cleavage and the reduction of the procaspase-3 and Bcl2. RA significantly reduced the production of tumor necrosis factor-α, IL-1β, and IL-6 on the TSLP-stimulated HMC-1 cells. In addition, RA significantly reduced the levels of IgE, IL-4, and TSLP in the short ragweed pollen-induced allergic conjunctivitis mouse model. In conclusion, the results of the study suggest that RA has a significant anti-inflammatory effect on TSLP-induced inflammatory reactions. These effects of RA are likely to be mediated through inhibiting the MDM2 increased by TSLP.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, 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, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Chan Lee
authors.initials: CL
authors.lastname: Park
authors.affiliation: Department of Computer Aided Mechanical Engineering, Sohae College, Jeonbuk, Gunsan 573-717, Republic of Korea. Electronic address: minho@sohae.ac.kr.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, 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, 20, Hoseo-ro 79beon-gil, Baebang-eup, Asan, Chungcheongnam-do 336-795, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D031164:Ambrosia / Q000276:immunology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology*; D003233:Conjunctivitis, Allergic / Q000188:drug therapy; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D000094632:Thymic Stromal Lymphopoietin; D000097123:Rosmarinic Acid
chemical_list: D053148:Caspase 3; D002934:Cinnamates; D016207:Cytokines; D053630:Depsides; D018793:Interleukin-13; D051736:Proto-Oncogene Proteins c-mdm2; D050800:STAT6 Transcription Factor; D000094632:Thymic Stromal Lymphopoietin; D000097123:Rosmarinic Acid; C494100:Stat6 protein, mouse; C497207:Mdm2 protein, mouse; C505409:Casp3 protein, mouse
keywords: Interleukin-13; Murine double minute 2; Rosmarinic acid; Signal transducer and activator of transcription 6; Thymic stromal lymphopoietin