2. Academic Validation
  3. Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase

Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase

  • Int Immunopharmacol. 2017 Oct:51:25-30. doi: 10.1016/j.intimp.2017.07.021.
Chien-An Chen 1,  Chien-Kuo Liu 2,  Ming-Ling Hsu 3,  Chih-Wen Chi 3,  Chun-Chuan Ko 3,  Jian-Syun Chen 4,  Cheng-Ta Lai 4,  Hen-Hong Chang 5,  Tzung-Yan Lee 6,  Yuen-Liang Lai 7,  Yu-Jen Chen 8
Affiliations

Affiliations

  • 1 Department of Radiation Oncology in Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 2 Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.
  • 3 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
  • 4 Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • 5 School of Post-Baccalaureate Traditional Chinese Medicine, College of Chinese Medicine, and Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
  • 6 Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 7 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan; Hospice and Palliative Care Center, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medical College, New Taipei City, Taiwan. Electronic address: [email protected].
  • 8 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan. Electronic address: [email protected].
PMID: 28772243 DOI: 10.1016/j.intimp.2017.07.021
Abstract

Daphnoretin, an active constituent of Wikstroemia indica C.A. Meys, has been shown possessing anti-cancer activity. In this study, we examined the effect of daphnoretin on differentiation and maturation of human myeloid dendritic cells (DCs). After treatment with daphnoretin (0, 1.1, 3.3, 10 and 30μM) to initiate monocytes, the recovery rate of DCs was reduced in a dose-dependent manner. The mature DCs differentiated in the presence of daphnoretin had fewer and shorter dendrites. Daphnoretin modulated DCs differentiation and maturation in terms of lower expression of CD1a, CD40, CD83, DC-SIGN, and HLA-DR. Daphnoretin inhibited the allostimulatory activity of DCs on proliferation of naive CD4+CD45+RA+ T cell. On the mitogen-activated protein kinase, daphnoretin down-regulated the lipopolysaccharide-augmented expression of phosphorylated c-Jun N-terminal kinase (pJNK), but not p38 and extracellular signal-regulated kinase 1/2 (ERK1/2). Activation of JNK by anisomycin reversed the effect of daphnoretin on daphnoretin-inhibited pJNK expression and dendrite formation of DCs. In disease model related to maturation of DCs, daphnoretin suppressed the acute rejection of skin allografts in mice. Our results suggest that daphnoretin modulated differentiation and maturation of DCs toward a state of atypical maturation with impaired allostimulatory function and this effect may go through down-regulation of phosphorylated JNK.

Keywords

Daphnoretin; Dendritic cell; Differentiation; JNK; Maturation.

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