Antiproliferative effects of TRPV1 ligands on nonspecific and enteroantigen-specific T cells from wild-type and Trpv1 KO mice.
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.
Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Mohammed-Samir
MS
Belmaáti
Sanne
S
Diemer
Tine
T
Hvarness
Katrine
K
Baumann
Anders E
AE
Pedersen
Rikke E
RE
Christensen
Mogens H
MH
Claesson
D000818:Animals; D000941:Antigens / Q000378:metabolism; D000982:Antipruritics / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D002211:Capsaicin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008024:Ligands; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D050916:TRPV Cation Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000235:genetics
D000941:Antigens; D000982:Antipruritics; D016207:Cytokines; D008024:Ligands; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D001613:beta 2-Microglobulin; D002211:Capsaicin