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Free Radic Biol Med ; 131: 309-317, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30578916

RESUMEN

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.


Asunto(s)
Ciclooctanos/farmacología , Células Dendríticas/efectos de los fármacos , Factores Inmunológicos/farmacología , Lignanos/farmacología , Compuestos Policíclicos/farmacología , Linfocitos T/efectos de los fármacos , Antígeno B7-2/genética , Antígeno B7-2/inmunología , Chlamydophila pneumoniae/crecimiento & desarrollo , Técnicas de Cocultivo , Ciclooctanos/aislamiento & purificación , Células Dendríticas/inmunología , Expresión Génica/efectos de los fármacos , Glutatión/inmunología , Glutatión/metabolismo , Antígenos HLA-DR/genética , Antígenos HLA-DR/inmunología , Humanos , Factores Inmunológicos/aislamiento & purificación , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lignanos/aislamiento & purificación , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Compuestos Policíclicos/aislamiento & purificación , Cultivo Primario de Células , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Schisandra/química , Linfocitos T/inmunología , Linfocitos T/microbiología , Células THP-1
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