Inhibition of TRPV1 Channel Activity in Human CD4+ T Cells by Nanodiamond and Nanoplatinum Liquid, DPV576

Abstract

Background: Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator. Here, we sought to examine the effect of DPV576 in modulating the functions of human CD4+ T lymphocytes and whether the modulation is mediated via TRPV channels. Materials and methods: Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:10 and 1:100 dilutions for 24 h in vitro. TRPV receptor expression (TRPV1 and TRPV4) on CD4+ T cells were examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. Results: DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28 resulted in decreased expression of the TRPV1 channel, but had no effect on TRPV4. This was accompanied by decreased secretion of IFN-γ and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of IFN-γ, and enhanced the secretion of IL-10. Conclusion: We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

“…In addition, DPV576 (a dispersed aqueous mixture composed of nanodiamond and nanoplatinum) activates human DCs and upregulates the levels of DC-secreted cytokine IL-10, 33 and we have recently observed that exposure of human CD4+ T lymphocytes to DPV576 inhibits the activity of the transient receptor potential vanilloid channel TRPV1 in CD4+ T lymphocytes, suggesting that it has the potential for use in pain management. 34 Work of others on the anti-inflammatory activity of several natural agents has also shown effects on IL-10 and DCs. Lippia sidoides , an aromatic shrub, can induce IL-10 production in THP-1 monocytes; 35 PureCell Complex (PCT)-233, an active molecular complex from Spinacia oleracea , increased IL-10 production but did not significantly modulate TNF release in alveolar macrophages treated with PCT-233 and budesonide after LPS stimulation; 36 and a complex mixture of herbal extracts has been shown to modulate the innate responsiveness of murine DCs.…”

Transient Receptor Potential Channels and Inflammatory Bowel Disease

“…In a sepsis model, the LPS-stimulated peritoneal macrophages showed an impaired phagocytosis when TRPV1 was knockout (36), suggesting the putative role of TRPV1 to potentiate macrophages. In CD4 + T cells, TRPV1 was associated with T cell receptor (TCR) and facilitated TCR-induced Ca 2+ inflow (37), and the activity of CD4 + T cells was impaired via the inhibition of TRPV1 (38). The activation of TRPV1 was also reported to enhance leukocyte rolling and adhesion (39).…”

Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

“…TRPV1 has been associated with T cell antigen receptor-induced calcium influx and signaling as well as non-canonical (MHC-independent) T cell activation in a mouse colitis model, in which it promotes T cell responses to increase intestinal inflammation [174]. Treatment of activated CD4 + T cells with DPV576 (an aqueous mixture of nanodiamond and nanoplatinum) resulted in specifically decreased expression of TRPV1 [394]. Ghoneum et al showed that this downregulation was accompanied by decreased IFN-γ secretion in capsaicin-activated CD4 + T cells [394].…”

“…Treatment of activated CD4 + T cells with DPV576 (an aqueous mixture of nanodiamond and nanoplatinum) resulted in specifically decreased expression of TRPV1 [394]. Ghoneum et al showed that this downregulation was accompanied by decreased IFN-γ secretion in capsaicin-activated CD4 + T cells [394]. T cells interact with macrophages and neutrophils, with these innate immune cells releasing cytokines that in turn modulate TRPV1 and TRPA1 [395,396].…”