Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress.

Autor: Martín-Hernández D; Servicio de Psiquiatría del Niño y del Adolescente, Instituto de Psiquiatría y Salud Mental, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain. davidmhbiotec@gmail.com.; CIBERSAM, Madrid, Spain. davidmhbiotec@gmail.com., Gutiérrez IL; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., González-Prieto M; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., MacDowell KS; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Robledo-Montaña J; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Tendilla-Beltrán H; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain.; Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico., Calleja-Rodríguez N; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Bris ÁG; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Ulecia-Morón C; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Moreno B; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Caso JR; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., García-Bueno B; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Rodrigues-Mascarenhas S; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain.; Laboratório de Imunobiotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba (UFPB), João Pessoa, Brazil., Marín-Jiménez I; Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Departamento de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain., Leza JC; CIBERSAM, Madrid, Spain.; Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Imas12, IUIN, Madrid, Spain., Menchén L; Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Departamento de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; CIBEREHD, Madrid, Spain.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Mar 08; Vol. 12 (1), pp. 4073. Date of Electronic Publication: 2022 Mar 08.
DOI: 10.1038/s41598-022-08011-8
Abstrakt: The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes and Sphk2. S1P accumulation could lead to inflammation and immune dysregulation reflected by upregulation of toll-like receptor 4 (TLR4) pathway, inhibition of anti-inflammatory mechanisms, cytokine-expression profile towards a T-helper lymphocyte 17 (Th17) polarization, plasmacytosis, decrease in IgA+ lymphoid lineage cells (CD45+)/B cells/plasmablasts, and increase in IgM+ B cells. Stress also enhanced intestinal permeability. Sphk2 knockout mice presented a cytokine-expression profile towards a boosted Th17 response, lower expression of claudin 3,4,7,8, and structural abnormalities in the colon. Intestinal pathophysiology should consider stress and S1P as modulators of the immune response. S1P-based drugs, including Sphk2 potentiation, represent a promising approach to treat IBD.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje