RT Journal Article
T1 Trimethylamine N-Oxide Promotes Autoimmunity and a Loss of Vascular Function in Toll-like Receptor 7-Driven Lupus Mice.
A1 Gonzalez-Correa, Cristina
A1 Moleon, Javier
A1 Miñano, Sofia
A1 Visitacion, Nestor de la
A1 Robles-Vera, Iñaki
A1 Gomez-Guzman, Manuel
A1 Jimenez, Rosario
A1 Romero, Miguel
A1 Duarte, Juan
K1 3,3-dimethyl-1-butanol
K1 cardiovascular complications
K1 hypertension
K1 systemic lupus erythematosus
K1 trimethylamine N-oxide
AB Plasma levels of trimethylamine N-oxide (TMAO) are elevated in lupus patients. We analyzed the implication of TMAO in autoimmunity and vascular dysfunction of the murine model of systemic lupus erythematosus (SLE) induced by the activation of the Toll-like receptor (TLR)7 with imiquimod (IMQ). Female BALB/c mice were randomly divided into four groups: untreated control mice, control mice treated with the trimethylamine lyase inhibitor 3,3-dimethyl-1-butanol (DMB), IMQ mice, and IMQ mice treated with DMB. The DMB-treated groups were administered the substance in their drinking water for 8 weeks. Treatment with DMB reduced plasma levels of TMAO in mice with IMQ-induced lupus. DMB prevents the development of hypertension, reduces disease progression (plasma levels of anti-dsDNA autoantibodies, splenomegaly, and proteinuria), reduces polarization of T lymphocytes towards Th17/Th1 in secondary lymph organs, and improves endothelial function in mice with IMQ-induced lupus. The deleterious vascular effects caused by TMAO appear to be associated with an increase in vascular oxidative stress generated by increased NADPH oxidase activity, derived in part from the vascular infiltration of Th17/Th1 lymphocytes, and reduced nrf2-driven antioxidant defense. In conclusion, our findings identified the bacterial-derived TMAO as a regulator of immune system, allowing for the development of autoimmunity and endothelial dysfunction in SLE mice.
PB MDPI AG
SN 2076-3921
YR 2021
FD 2021-12-29
LK http://hdl.handle.net/10668/20768
UL http://hdl.handle.net/10668/20768
LA en
NO González-Correa C, Moleón J, Miñano S, Visitación N, Robles-Vera I, Gómez-Guzmán M, et al. Trimethylamine N-Oxide Promotes Autoimmunity and a Loss of Vascular Function in Toll-like Receptor 7-Driven Lupus Mice. Antioxidants (Basel). 2021 Dec 30;11(1):84.
DS RISalud
RD Apr 11, 2025