Involvement of heme oxygenase-1 in suppression of T cell activation by quercetin.
Immunopharmacol Immunotoxicol
; 42(4): 295-305, 2020 Aug.
Article
in En
| MEDLINE
| ID: mdl-32397768
ABSTRACT
AIM:
Acute rejection is still a major problem in transplantation and one of the most important causes of late graft loss. Cyclosporine and tacrolimus are widely used for suppression of T cell function to avoid graft rejection, but long-term use of these compounds is associated with serious toxicities. Quercetin, a flavonoid found in fruits and vegetables, has been demonstrated to exhibit cytoprotective effects through the induction of heme oxygenase (HO) -1, an enzyme involved in heme catabolism. We hypothesized that quercetin induces HO-1 in T cells and suppresses T cell function via HO-1. In the present study, we showed that quercetin suppressed the A23187-mediated expression of interleukin (IL) -2 in T cells.METHODS:
Mouse splenocytes, enriched T cells, and EL4 cells, a mouse T cell line, were treated with quercetin, and then stimulated with A23187, a calcium ionophore, concanavalin A, or anti-CD3ε and anti-CD28 antibodies. Cell proliferation, expression of IL-2, calcium mobilization, apoptosis, cell cycle, and phosphorylation of extracellular signal-regulated kinase (ERK) were investigated.RESULTS:
Quercetin induced HO-1, and this induction of HO-1 was implicated in the suppression of IL-2 production. Furthermore, the induction of HO-1 by quercetin suppressed the influx of calcium ions, a known trigger of IL-2 production. Additionally, quercetin suppressed T cell proliferation through promotion of cell cycle arrest via HO-1 induction, but quercetin did not induce apoptosis. To investigate the role of the signal transduction pathway in quercetin's effect on cell proliferation, we evaluated the phosphorylation of ERK in T cells. Quercetin suppressed the A23187-mediated stimulation of ERK, an effect that was mediated through HO-1. These results suggested that HO-1 is involved in the suppressive effects of quercetin on T cell activation and proliferation.CONCLUSION:
Our findings indicate that the quercetin may be a promising candidate for inducing HO-1 in T cells, thereby facilitating immunosuppressive effects.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quercetin
/
T-Lymphocytes
/
Heme Oxygenase-1
/
Antioxidants
Limits:
Animals
Language:
En
Journal:
Immunopharmacol Immunotoxicol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
Japón