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

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• 作者：Myoung-schook Yoou^a ; Chan Lee Park^a ; Min-Ho Kim^b ; ^{minho@sohae.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Hyung-Min Kim^a ; ^{hmkim@khu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Hyun-Ja Jeong^c ; ^{hjjeong@hoseo.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Rosmarinic acid ; Thymic stromal lymphopoietin ; Murine double minute 2 ; Signal transducer and activator of transcription 6 ; Interleukin-13
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：771
• 期：Complete
• 页码：191-198
• 全文大小：1408 K

文摘

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.