Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.
Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-β) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-β and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated).
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala S/N, 11340 México City, Mexico. jahesa7591@gmail.com.|Departamento de Genética y Biología Molecular, CINVESTAV, Avenida Instituto Politécnico Nacional Número 2508, 07360 México City, Mexico. jahesa7591@gmail.com.
Sonia
S
López-García
Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Calzada del Hueso Número 1100, 04960 México City, Mexico. jorge.encb@yahoo.com.mx.
Jorge Ismael
JI
Castañeda-Sanchez
Centro Médico Nacional Siglo XXI, IMSS, Unidad de Investigación Médica en Farmacología, Avenida Cuauhtémoc Número 330, 06725 México City, Mexico. adelinajim08@prodigy.net.mx.
Adelina
A
Jiménez-Arellanes
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala S/N, 11340 México City, Mexico.
Lilia
L
Domínguez-López
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala S/N, 11340 México City, Mexico.
Maria Eugenia
ME
Castro-Mussot
Departamento de Genética y Biología Molecular, CINVESTAV, Avenida Instituto Politécnico Nacional Número 2508, 07360 México City, Mexico. jahesa7591@gmail.com.
Javier
J
Hernández-Sanchéz
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala S/N, 11340 México City, Mexico. julietalunah@hotmail.com.
Julieta
J
Luna-Herrera
D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D009569:Nitric Oxide / Q000096:biosynthesis; D009828:Oleanolic Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014315:Triterpenes / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097245:Ursolic Acid
D009569:Nitric Oxide; D009828:Oleanolic Acid; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000097245:Ursolic Acid
CD36; TGR5; macrophages; nitric oxide (NO); oleanolic acid; reactive oxygen species (ROS); transforming growth factor (TGF-β); triterpenes; tuberculosis; tumor necrosis factor (TNF-α); ursolic acid