Induction on differentiation and modulation of bone marrow progenitor of dendritic cell by methionine enkephalin (MENK)

Cancer Immunol Immunother. 2012 Oct;61(10):1699-711. doi: 10.1007/s00262-012-1221-9. Epub 2012 Mar 6.


Methionine enkephalin (MENK), the endogenous neuropeptide, is known to exert direct effects on the neuroendocrine and the immune systems and participates in regulation of various functions of cells related to both the innate and adaptive immune systems. Dendritic cells (DCs) play important role in initiating and regulating T cell responses. The aim of this work is to investigate the effects of MENK on differentiation, maturation, and function of DCs derived from murine bone marrow progenitors (BM-derived DCs). Our result showed that MENK could induce BM-derived DCs to polarize predominantly to mDC subtype, rather than pDC both in vivo and in vitro, and this was in favor of Th1 response. BM-derived DCs, after treatment with MENK, up-regulated the expressions of MHC class II and key costimulatory molecules. Result by RT-PCR showed MENK could increase expressions of delta and kappa receptors on BM-derived DCs. Also MENK promoted BM-derived DCs to secret higher levels of proinflammatory cytokines of IL-12p70, TNF-α. Furthermore, differentiated BM-derived DCs treated with MENK displayed higher activity to induce allogeneic T cell proliferation and MENK also inhibited tumor growth in vivo and induced apoptosis of tumor cells in vitro. Thus, it is concluded that MENK could be an effective inducer of BM-derived DCs and might be a new therapeutic agent for cancer, as well as other immune handicapped disease. Also we may consider MENK as a potential adjuvant in vaccine preparation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Marrow Cells / drug effects*
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Enkephalin, Methionine / pharmacology*
  • Female
  • Genes, MHC Class II / drug effects
  • Humans
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / pharmacology*
  • Receptors, Opioid, delta / biosynthesis
  • Receptors, Opioid, kappa / biosynthesis
  • Stem Cells / drug effects*
  • Up-Regulation / drug effects


  • Cytokines
  • Neurotransmitter Agents
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Enkephalin, Methionine