Antiproliferative effects of TRPV1 ligands on nonspecific and enteroantigen-specific T cells from wild-type and Trpv1 KO mice

Inflamm Bowel Dis. 2014 Jun;20(6):1004-14. doi: 10.1097/MIB.0000000000000039.

Abstract

Background: Treatment with the TRPV1 agonist, capsaicin, was previously shown to protect against experimental colitis in the severe combined immunodeficiency (SCID) T-cell transfer model. Here, we investigate trpv1 gene expression in lymphoid organs and cells from SCID and BALB/c mice to identify a potential target for the anti-inflammatory effect of capsaicin.

Methods: The trpv1 expression was studied by real-time PCR in lymphoid tissues and gut of untreated and capsaicin-treated colitic SCID mice. Effects of capsaicin and a TRPV1 antagonist on T cells were studied in vitro.

Results: In contrast to BALB/c mice, spleen, lymph nodes, and rectum of colitic and noncolitic SCID mice express trpv1 mRNA. Capsaicin treatment in vivo attenuated T-cell transfer colitis and capsaicin in vitro also attenuated T-cell proliferation induced by enteroantigen, mitogen, and anti-CD3/CD28 beads in BALB/c, C57BL/6 mice, and B6.129X1-trpv1tm1Jul/J trpv1 knockout mice. Proliferation and cytokine secretion were fully comparable in mice with and without trpv1 expression. Likewise, enteroantigen- and mitogen-stimulated T cells from wild-type and trpv1 knockout mice were equally inhibited by capsaicin. Surprisingly, the TRPV1 antagonist BCTC also inhibited enteroantigen- and mitogen-induced T-cell proliferation.

Conclusions: The trpv1 mRNA expression in lymphoid organs and the rectum of SCID mice suggests that the TRPV1 signaling in these organs could play a role in capsaicin-mediated attenuation of colitis. In addition, capsaicin-induced inhibition of T-cell proliferation of wild-type T cells lacking trpv1 expression suggests that capsaicin inhibits colitogenic T cells in a TRPV1 receptor-independent way, which might be linked to its anti-inflammatory effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Antipruritics / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation
  • Capsaicin / pharmacology*
  • Cell Proliferation / drug effects
  • Colitis / drug therapy*
  • Colitis / immunology
  • Colitis / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ligands
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Pyrazines / pharmacology
  • Pyridines / pharmacology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • beta 2-Microglobulin / genetics

Substances

  • Antigens
  • Antipruritics
  • Cytokines
  • Ligands
  • N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide
  • Pyrazines
  • Pyridines
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • beta 2-Microglobulin
  • Capsaicin