Inhibition of MDM2 expression by rosmarinic acid in TSLP-stimulated mast cell

Eur J Pharmacol. 2016 Jan 15:771:191-8. doi: 10.1016/j.ejphar.2015.12.025. Epub 2015 Dec 13.

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.

Keywords: Interleukin-13; Murine double minute 2; Rosmarinic acid; Signal transducer and activator of transcription 6; Thymic stromal lymphopoietin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambrosia / immunology
  • Animals
  • Caspase 3 / metabolism
  • Cell Line
  • Cinnamates / pharmacology*
  • Conjunctivitis, Allergic / drug therapy
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Depsides / pharmacology*
  • Humans
  • Interleukin-13 / biosynthesis
  • Mast Cells / metabolism*
  • Mice
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-mdm2 / biosynthesis*
  • Rosmarinic Acid
  • STAT6 Transcription Factor / biosynthesis
  • STAT6 Transcription Factor / genetics
  • Thymic Stromal Lymphopoietin

Substances

  • Cinnamates
  • Cytokines
  • Depsides
  • Interleukin-13
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Casp3 protein, mouse
  • Caspase 3
  • Thymic Stromal Lymphopoietin