title: Tryptanthrin reduces mast cell proliferation promoted by TSLP through modulation of MDM2 and p53.
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.
  
  
  CONCLUSIONS
  Our results suggest that TR determined with new concept has intensive potential for the treatment of mast cell-mediated allergic diseases, such as AD.
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: Na-Ra
authors.initials: NR
authors.lastname: Han
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 79 beon-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: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D016207:Cytokines; D018793:Interleukin-13; D019394:Ki-67 Antigen; D011799:Quinazolines; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C415350:interleukin-7 receptor, alpha chain; C046243:tryptanthrine; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; D000094632:Thymic Stromal Lymphopoietin
keywords: Mast cells; Mouse double minute 2; Proliferation; Thymic stromal lymphopoietin; Tryptanthrin