Functional modulation of the pathway between dendritic cells (DCs) and CD4+T cells by the neuropeptide: Methionine enkephalin (MENK)

Synergistic effect of methionine encephalin (MENK) combined with pidotimod(PTD) on the maturation of murine dendritic cells (DCs)

“…Our major findings were as evidenced as: (1) When treated with 10 -12 M MENK plus 1.1 μg/ml PTD for 48 h, the number of BMDCs could remarkably increase and show more maturation than those treated with either MENK or PTD alone; (2) The co-stimulatory molecules CD80, CD86, CD40, followed by antigen-presenting molecules MHC-II and CD83, increased significantly. However, there was no statistically significant difference of the BMDC phenotype for 24 h. The authors 27 in my group showed that a 24 h-incubation of DC2.4 cell line with MENK alone did induce significantly higher expression of maturational surface markers. This was due to the use of established cell line; (3) FITC-dextran uptaking and ACP testing were used to evaluate the antigen-uptake capability, which is characteristic of immature DCs.The addition of 10 -12 M MENK plus 1.1 μg/ml PTD to the BMDC cultures decreased the number of DAB precipitation and the content of ACP, indicating lowering of the antigen uptaking capability; (4) Both phenotypic and functional findings were in concert with higher expression of IL-12 and TNF-α and promote the proliferation of lymphocytes.…”

“…31,34,[36][37][38][39] Our previous work has proven that MENK could intensify in the DC-CD4+T cell pathway, stimulate proliferation of lymphocytes in human peripheral blood, induce DC progenitors to develop to mDC, and drive macrophage polarization into M1-type in mice bearing tumor. 27,[40][41][42] PTD, a synthetic substance, has been shown to ameliorate different functions of innate and adaptive immune responses both in animals and humans. 28 It has been reported that PTD was able to enhance the effectors of the innate immunity responses by potentiating different functions of the professional phagocytes and NK cell activity; PTD also significantly increased the proliferation of spleen cells in response to Con-A and interleukin-2 (IL-2) stimulation.…”

“…[21][22][23][24][25] Both MENK and PTD are peptide molecules of TH1 modulatiors, 5,16 and each of these peptides, when used separately, promotes functional maturation of dendritic cells and have a marked effect on suppressing the progression of some tumors. 26,27 Whether these two peptides exert synergistic effect on DCs remains unclear so far. The purpose of this study was to investigate the effect of MENK, when combined with PTD on maturation of DC, to provide a key reference for combined use of them in clinical treatment or preparation of vaccines.…”

Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs)

“…[15][16][17][18][19][20][21] Our documented record showed that considerable work of approaches with MENK on its impact on immune cells in vitro and in vivo has been done in our laboratory. [7][8][9][10][11] There are predominantly mu, delta, and kappa-3 types of opioid receptors. The mu receptor is responsible for addiction and pain, while kappa and delta are responsible for immunity according to published data.…”

“…2 The data from both early documented studies [3][4][5] and published results in our laboratory indicated that MENK at suitable range of concentrations could enhance activity of various types of immune cells, like: augmenting interactions between dendritic cells (DCs) and CD4+T cells, induction of phenotypic and functional maturation of DCs with increased antigen presentation, improvement of antitumor activity of DCs loaded with antigen, induction of macrophage polarization to the M1 phenotype in mouse model, eliciting CD8+T cell cytotoxicity, upregulating the secretion of cytokines such as IL-2, IL-12, IFN-γ, TNF-α, increasing the release of hydrogen peroxide and nitric oxide and stimulation of lymphocyte subpopulations in normal human donors. [6][7][8][9][10][11][12] In addition, there have been studies indicating that MENK could inhibit tumor growth. 13,14 However, so far there is little approach to the influence on lymphocyte subpopulations in large samples of cancer patients by MENK.…”