The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans

Orally ingested probiotic bacteria are able to modulate the immune system. However, differences exist in the immunomodulatory effects of different probiotic strains. Moreover, different regulatory effects, which depend on the health status of the consumer, have been identified. This work describes a randomized, doubleblind, placebo-controlled human clinical trial to investigate the immune effects on healthy people of a fermented product containing two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, which was compared with another fermented product, a standard yogurt. Consumption of either the new product or yogurt increased the proportion of phagocytic cells, including monocytes and neutrophils, as well as their phagocytic activity. However, combination of the product containing the strains L. gasseri CECT 5714 and L. coryniformis CECT 5711 also induced an increase in the proportion of natural killer (NK) cells and in IgA concentrations. The effects were higher after two weeks of treatment than after 4 weeks, which suggests regulation of the immune system. In addition, the new product enhanced immunity in the participants to a greater extent than did the control standard yogurt. [Int Microbiol 2006; 9(1):47-52

The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans

Orally ingested probiotic bacteria are able to modulate the immune system. However, differences exist in the immunomodulatory effects of different probiotic strains. Moreover, different regulatory effects, which depend on the health status of the consumer, have been identified. This work describes a randomized, doubleblind, placebo-controlled human clinical trial to investigate the immune effects on healthy people of a fermented product containing two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, which was compared with another fermented product, a standard yogurt. Consumption of either the new product or yogurt increased the proportion of phagocytic cells, including monocytes and neutrophils, as well as their phagocytic activity. However, combination of the product containing the strains L. gasseri CECT 5714 and L. coryniformis CECT 5711 also induced an increase in the proportion of natural killer (NK) cells and in IgA concentrations. The effects were higher after two weeks of treatment than after 4 weeks, which suggests regulation of the immune system. In addition, the new product enhanced immunity in the participants to a greater extent than did the control standard yogurt.This work was supported by Puleva Biotech SA. Federico Lara-Villoslada and Saleta Sierra are recipients of a fellowship from the Fundación Universidad-Empresa, Universidad de Granada, Spain. Rocío Martín is recipient of a grant from the Comunidad de Madrid, Spain

Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation of concentrative nucleoside transporters Cnt1 and Cnt2 through tumor necrosis factor-alpha-dependent and -independent mechanisms

In murine bone marrow macrophages, lipopolysaccharide (LPS) induces apoptosis through the autocrine production of tumor necrosis factor-alpha (TNF-alpha), as demonstrated by the fact that macrophages from TNF-alpha receptor I knock-out mice did not undergo early apoptosis. In these conditions LPS up-regulated the two concentrative high affinity nucleoside transporters here shown to be expressed in murine bone marrow macrophages, concentrative nucleoside transporter (CNT) 1 and 2, in a rapid manner that is nevertheless consistent with the de novo synthesis of carrier proteins. This effect was not dependent on the presence of macrophage colony-stimulating factor, although LPS blocked the macrophage colony-stimulating factor-mediated up-regulation of the equilibrative nucleoside transport system es. TNF-alpha mimicked the regulatory response of nucleoside transporters triggered by LPS, but macrophages isolated from TNF-alpha receptor I knock-out mice similarly up-regulated nucleoside transport after LPS treatment. Although NO is produced by macrophages after LPS treatment, NO is not involved in these regulatory responses because LPS up-regulated CNT1 and CNT2 transport activity and expression in macrophages from inducible nitric oxide synthase and cationic amino acid transporter (CAT) 2 knock-out mice, both of which lack inducible nitric oxide synthesis. These data indicate that the early proapoptotic responses of macrophages, involving the up-regulation of CNT transporters, follow redundant regulatory pathways in which TNF-alpha-dependent- and -independent mechanisms are involved. These observations also support a role for CNT transporters in determining extracellular nucleoside availability and modulating macrophage apoptosis

Efficacy of Vafidemstat in Experimental Autoimmune Encepha-Lomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis

Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A forms a part of protein complexes that regulate the expression of genes involved in the onset and progression of diseases such as cancer, central nervous system (CNS) disorders, viral infections, and others. Vafidemstat (ORY-2001) is a clinical stage inhibitor of KDM1A in development for the treatment of neurodegenerative and psychiatric diseases. However, the role of ORY-2001 targeting KDM1A in neuroinflammation remains to be explored. Here, we investigated the effect of ORY-2001 on immune-mediated and virus-induced encephalomyelitis, two experimental models of multiple sclerosis and neuronal damage. Oral ad-ministration of ORY-2001 ameliorated clinical signs, reduced lymphocyte egress and infiltration of immune cells into the spinal cord, and prevented demyelination. Interestingly, ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the inflammatory gene expression signature characteristic ofEAE in the CNS of mice more potently. In addition, ORY-2001 induced gene expression changes con-cordant with a potential neuroprotective function in the brain and spinal cord and reduced neuronal glutamate excitotoxicity-derived damage in explants. These results pointed to ORY-2001 as a promising CNS epigenetic drug able to target neuroinflammatory and neurodegenerative diseases and provided preclinical support for the subsequent design of early-stage clinical trials.This research funded by Oryzon Genomics, S.A. and partially supported by RETOS: (RTC2016-4955-1); EUROSTAR II: EMTherapy (CIIP-20152001/E!9683) and CDTI: EDOTEM (IDI-20180117)

La expresión de IL-10 interviene en la regulación de la respuesta inflamatoria por los ácidos grasos omega 3

Objetivo o antecedente: Los ácidos grasos poliinsaturados son importantes para el organismo humano debido a su implicación en numerosas funciones biológicas. Las dietas occidentales se caracterizan por ser excesivamente ricas en ácidos grasos w-6 y pobres en ácidos grasos w-3. Los ácidos grasos de la serie w-3 son necesarios para el normal crecimiento y desarrollo del individuo así como para la regulación de la respuesta inmunológica. El objetivo de este estudio es analizar el efecto de una dieta enriquecida en ácidos grasos w-3 frente a un proceso inflamatorio así como el estudio de los mecanismos implicados en dicho efecto. Intervenciones: Para ello, ratones Balb/c fueron alimentados durante un mes con una dieta cuya fuente lipídica era 100% aceite de girasol (control), o con la misma dieta en la que el 12% de la grasa era aceite de pescado y el resto aceite de girasol (W-3). Doce horas antes de su sacrificio se indujo en una de las orejas de cada animal una dermatitis de contacto que cursó con inflamación y edema. Como agente inflamatorio se utilizó 2,4 dinitrofluorobenceno. Tras el sacrificio se tomaron diversas muestras y se analizaron. Resultados: La inflamación, medida como peso y contenido de agua de las orejas, disminuyó significativamente en los ratones alimentados con w-3. La medida de la infiltración leucocitaria y los parámetros de oxidación revelaron también la mejora en el proceso inflamatorio de dichos ratones. Para explicar estos hechos se analizó la expresión de diversas citocinas, observándose un incremento de IL-10 y una disminución de citocinas tanto Th1 como Th2. Conclusiones: Los ácidos grasos w-3 poseen un efecto inmunomodulador al actuar como antiinflamatorios y antialérgicos, al tiempo que aumentan algunas defensas del organismo. La citocina reguladora IL-10 podría ser la responsable del efecto antiinflamatorio ejercido por los ácidos grasos w-3