Tetrandrine inhibits differentiation of proinflammatory subsets of T helper cells but spares de novo differentiation of iTreg cells

Int Immunopharmacol. 2019 Apr:69:307-312. doi: 10.1016/j.intimp.2019.01.040. Epub 2019 Feb 12.

Abstract

Tetrandrine (TET) is an anti-inflammatory compound isolated from Chinese herb Stephania tetrandra S. Moore. It was reported recently that the differentiation of Th17 cells was inhibited, while the generation of induced Treg cells (iTregs) was promoted, by TET treatment. We therefore carefully examined the effect of TET on the differentiation of four major subsets of T helper cells. The results showed that in vitro treatment with TET potently inhibited the differentiation of Th1, Th2 and Th17 cells. Administration of LPS resulted in a mixed Th1, Th2 and Th17 responses in normal mice, and such effect of LPS was inhibited by in vivo TET treatment as well. In contrast, TET did not promote or inhibit the in vitro generation of iTregs from naïve CD4+CD25-Foxp3/gfp- T cells. Furthermore, spontaneous and rapamycin-induced conversion of naïve CD4+CD25-Foxp3/gfp- T cells into Foxp3-expressing iTregs in congenic mice was not affected by TET treatment. Thus, TET had the capacity to inhibit the differentiation of proinflammatory Th1, Th2 and Th17 cells, while sparing the generation of Tregs. As a Treg-friendly and broad spectrum anti-inflammatory agent, the molecular mechanism and the therapeutic potential of TET in various human inflammatory diseases should be further studied.

Keywords: Tetrandrine; Th1 cells; Th17 cells; Th2 cells; iTreg cells.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzylisoquinolines / therapeutic use*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Drugs, Chinese Herbal
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred C57BL
  • Stephania tetrandra / immunology
  • T-Lymphocytes, Helper-Inducer / physiology*
  • T-Lymphocytes, Regulatory / physiology*
  • Th17 Cells / physiology*

Substances

  • Anti-Inflammatory Agents
  • Benzylisoquinolines
  • Cytokines
  • Drugs, Chinese Herbal
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Lipopolysaccharides
  • tetrandrine