Journal of Cellular and Molecular Medicine | |
MLK3 is a novel target of dehydroglyasperin D for the reduction in UVB‐induced COX‐2 expression in vitro and in vivo | |
Sung Keun Jung1  Su Jeong Ha4  Yeong A Kim1  Jihoon Lee1  Tae-Gyu Lim1  Yun Tai Kim4  Nam Hyouck Lee4  Jun Seong Park2  Myeong-Hun Yeom2  Hyong Joo Lee3  | |
[1] WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Korea;Skin Research Institute, Amorepacific R&D Center, Yongin, Korea;Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Korea;Division of Metabolism and Functionality Research, Korea Food Research Institute, Seongnam, Korea | |
关键词: dehydroglyasperin D; cyclooxygenase‐2; mixed‐lineage kinase 3; licorice; inflammation; | |
DOI : 10.1111/jcmm.12311 | |
来源: Wiley | |
【 摘 要 】
Dehydroglyasperin D (DHGA-D), a compound present in licorice, has been found to exhibit anti-obesity, antioxidant and anti-aldose reductase effects. However, the direct molecular mechanism and molecular targets of DHGA-D during skin inflammation remain unknown. In the present study, we investigated the effect of DHGA-D on inflammation and its mechanism of action on UVB-induced skin inflammation in HaCaT human keratinocytes and SKH-1 hairless mice. DHGA-D treatment strongly suppressed UVB-induced COX-2 expression, PGE2 generation and AP-1 transactivity in HaCaT cells without affecting cell viability. DHGA-D also inhibited phosphorylation of the mitogen-activated protein kinase kinase (MKK) 3/6/p38, MAPK/Elk-1, MKK4/c-Jun N-terminal kinase (JNK) 1/2/c-Jun/mitogen, and stress-activated protein kinase (MSK), whereas phosphorylation of the mixed-lineage kinase (MLK) 3 remained unaffected. Kinase and co-precipitation assays with DHGA-D Sepharose 4B beads showed that DHGA-D significantly suppressed MLK3 activity through direct binding to MLK3. Knockdown of MLK3 suppressed COX-2 expression as well as phosphorylation of MKK4/p38 and MKK3/6/JNK1/2 in HaCaT cells. Furthermore, Western blot assay and immunohistochemistry results showed that DHGA-D pre-treatment significantly inhibits UVB-induced COX-2 expression in vivo. Taken together, these results indicate that DHGA-D may be a promising anti-inflammatory agent that mediates suppression of both COX-2 expression and the MLK3 signalling pathway through direct binding and inhibition of MLK3.Abstract
【 授权许可】
CC BY
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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