Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest

Int Immunopharmacol. 2015 Jun;26(2):328-37. doi: 10.1016/j.intimp.2015.04.019. Epub 2015 Apr 21.

Abstract

Pogostone (PO) is one of the major chemical constituents of the essential oil of Pogostemon cablin (Blanco) Benth. In the present study, the effect of PO on T cell responsiveness was investigated to explore its potential in immunosuppression by a Concanavalin A (ConA)-stimulation model using splenocytes isolated from C57BL/6 mice. Cytotoxicity by PO on normal splenocytes was evaluated by MTS assays. Characteristics of apoptosis, proliferation, and cell cycle were analyzed by flow cytometry. Related expressions of cyclins and cyclin-dependent kinases (CDKs) were also determined by flow cytometry. Inflammatory cytokine profiling was performed emplying cytometric beads assays (CBA). Moreover, the T cell-mediated delayed Type hepersensity (DTH) model was applied to evaluate the immunosuppressive activity of PO. Neither viability reduction in normal splenocytes nor apoptosis in ConA-stimulated splenocytes was observed under PO treatments. Meanwhile, PO remarkably reduced the total population of ConA-stimulated T cell, blocked T cell proliferation induced by Con A, and inhibited the production of IFN-γ and IL-10. This blockade of stimulated T cell proliferation by PO was likely attributed to down-regulation of cyclin E, cyclin B and CDK1 and the subsequent S-phase arrest. Additionally, PO could inhibit the DTH reaction by alleviating ear swelling and inflammatory infiltrations in the DNCB-challenged ear. Taken together, PO exhibited an immunosuppressive property by directly blocking T cell proliferation as well as altering inflammatory cytokine profile, suggesting that PO may have clinical implications for treating autoimmune diseases and other immune-based disorders.

Keywords: Cell cycle; Immunosuppression; Pogostone; S phase arrest; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cytokines / metabolism
  • Hypersensitivity, Delayed / chemically induced
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / prevention & control*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Inflammation Mediators / metabolism
  • Lamiaceae / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oils, Volatile / administration & dosage*
  • Oils, Volatile / adverse effects
  • S Phase Cell Cycle Checkpoints* / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Cyclin B
  • Cyclin E
  • Cytokines
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Oils, Volatile
  • Pogostone
  • CDC2 Protein Kinase