13 research outputs found

    Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells.

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    A strain of lactic acid bacteria, Lactobacillus paracasei KW3110 (KW3110), activates M2 macrophages with anti-inflammatory reactions and mitigates aging-related chronic inflammation and blue-light exposure-induced retinal inflammation in mice. However, the mechanism underlying the anti-inflammatory effects of KW3110 remains unclear. In this study, we investigated the anti-inflammatory effects of KW3110 using both mouse and human immune cells and evaluated the suppressive effect of KW3110 on the inflammatory reactions of the cells stimulated with lipopolysaccharide and adenosine 5'-triphosphate (LPS/ATP). KW3110 treatment induced anti-inflammatory cytokine interleukin (IL)-10 production in the supernatants of murine macrophage-like cells, J774A.1, and suppressed IL-1β production in the supernatants of LPS/ATP-stimulated cells. The influence of KW3110 on the production of these cytokines was inhibited by pre-treatment with phagocytosis blocker or transfection with siRNAs for IL-10 signaling components. KW3110 treatment also suppressed activation of caspase-1, an active component of inflammasome complexes, in LPS/ATP-stimulated J774A.1 cells, and its effect was inhibited by transfection with siRNAs for IL-10 signaling components. In addition to the effects of KW3110 on J774A.1 cells, KW3110 treatment induced IL-10 production in the supernatants of human monocytes, and KW3110 or IL-10 treatment suppressed caspase-1 activation and IL-1β production in the supernatants of LPS/ATP-stimulated cells. These results suggest that KW3110 suppresses LPS/ATP stimulation-induced caspase-1 activation and IL-1β production by promoting IL-10 production in mouse and human immune cells. Our findings reveal a novel anti-inflammatory mechanism of LAB and the effect of KW3110 on caspase-1 activation is expected to contribute to constructing future preventive strategies for inflammation-related disorders using food ingredients

    Oral administration of Lactococcus lactis subsp. lactis JCM5805 enhances lung immune response resulting in protection from murine parainfluenza virus infection.

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    When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer's patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo

    <i>Lactobacillus paracasei</i> KW3110 Prevents Inflammatory-Stress-Induced Mitochondrial Dysfunction in Mouse Macrophages

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    Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects, including the prevention of blue light exposure induced retinal inflammation and ageing-related chronic inflammation in mice. The mechanism involves the promotion of anti-inflammatory cytokine interleukin (IL)-10 production by KW3110, leading to reduced pro-inflammatory cytokine IL-1β production. Although various stress-induced mitochondrial damages are associated with excessive inflammatory responses, the effect of KW3110 on inflammatory-stress-induced mitochondrial damage remains unknown. In this study, we investigated the effect of KW3110 on inflammatory stress-induced mitochondrial damage using the murine macrophage-like cell line J774A.1. KW3110 treatment suppressed lipopolysaccharide (LPS)-induced mitochondrial dysfunction, including downregulation of membrane potential, induction of reactive oxygen species, and respiratory dysfunction. In addition, KW3110 prevented LPS-induced disruption of mitochondrial morphology including cristae structures. IL-10 treatment also ameliorated LPS-induced mitochondrial dysfunction and morphology disruption. These results suggest that KW3110 prevents LPS-induced mitochondrial dysfunction, potentially via promoting IL-10 production in mouse macrophages. We are the first to reveal a suppressive effect of lactic acid bacteria on mitochondrial morphology disruption in inflammatory-stressed macrophages. Our findings contribute to understanding inflammatory-stress-induced mitochondrial damage and developing food ingredients with preventive effects on mitochondrial-damage-derived inflammatory conditions

    Characterization of genomic DNA of lactic acid bacteria for activation of plasmacytoid dendritic cells

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    Abstract Background Lactococcus lactis strain Plasma (LC-Plasma) possesses strong stimulatory activity for plasmacytoid dendritic cells (pDCs) via the TLR9-Myd88 pathway. To reveal the effective lactic acid bacteria (LAB) genome structure for pDCs stimulatory activity, we performed in vitro screening, using randomly selected 200 bp DNA fragments from the LC-Plasma genome. Results We found that the CpG motif copy number in the fragments was positively and significantly correlated with pDCs stimulatory activity (R = 0.491, p < 0.01). However, the determination coefficient (R 2 ) was 0.24, which means other factors affecte activity. We found that the G + C contents of the fragment showed a significant negative correlation with activity (R = − 0.474, p < 0.01). The correlation between pDCs stimulatory activity and the copy number of CpG motifs was greatly increased when DNA fragments were stratified by G + C contents. We also performed bioinformatics analysis and a screening of LAB strains with high pDCs stimulatory activity. Species with a high copy number of CpG motifs in the low-G + C region of their genomes had higher probability of inducing high-pDCs stimulatory activity. L. lactis subsp. lactis, Leuconostoc mesenteroides, and Pediococcus pentosaceus were three typical examples of LAB that had high pDCs stimulatory activity. Conclusions Our data suggested that the G + C content of DNA is one of the critical factors for pDCs stimulatory activity by DNA fragments. Furthermore, we found that the copy number in the low-G + C regions strongly affected the pDCs stimulatory activity of whole cells of LAB strains. These results should be useful for the design of new DNA fragments containing CpG motifs. This study also demonstrated an in silico screening method for identifying bacterial species that are able to activate pDCs

    Activation of pDCs in intestine by JCM5805 administration.

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    <p>Healthy C57BL / 6J mice were divided into control and JCM5805 groups (n = 4 in each group), and mice in the JCM5805 group were orally administered JCM5808 daily for 2 weeks. A. Low density cells prepared from PP of each group were analyzed by FACS. Expression level of cell surface activation marker was evaluated for MHC class II as median fluorescence intensities (M.F.I.) in left panel. Ratio of pDCs to total population was shown in right panel. pDCs was defined as “CD3<sup>−</sup> Siglec-H<sup>+</sup> CD11c<sup>+</sup> in total population”. Short line represents the mean values. *<i>P</i><0.05 (Student’s t test). B, Total mRNA was extracted from PP pDCs from mice in the control (open columns) and JCM5805 groups (dot columns) (n = 8 in each group). <i>Ifnα</i> and <i>Ifnβ</i> gene expressions were measured by qRT-PCR and normalized to <i>Gapdh</i> gene expression. Data are shown as mean ± SD. *<i>P</i><0.05 (Student’s t test). These data are representative of three independent experiments. Each data are mean ± SD.</p

    Effects of JCM5805 on mPIV1 infection.

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    <p>A. Experimental procedure of mPIV1 infection. Mice in the control and JCM5805 groups were fed diet with or without 1 mg / mouse / day of JCM5808 during the study period (day -14 to 15). Mice were intranasally infected with mPIV1 on day 0. On 3 days post-mPIV1 infection, six mice were sacrificed from each group for lung histopathology. Thereafter survival rate, body weight and clinical scores were investigated with remained control mice n = 12, and JCM5805 mice n = 13. B. Survival rate of mice infected with mPIV1. The control (circle) and JCM5805 (square) groups consisted of 12 and 13 mice, respectively. The survival of each animal was monitored daily. <i>P</i><0.001 (Log-Rank test). C. Body weight of mice infected with mPIV1. The control (circle) and JCM5805 (square) groups consisted of 12 and 13 mice, respectively. The body weight of each surviving animal was measured daily. The body weight values are shown as mean ± SD. *<i>P</i><0.05, **<i>P</i><0.01 (Student’s t test). The data shown is representative of two independent experiments.</p

    Lactobacillus paracasei KW3110 Suppresses Inflammatory Stress-Induced Premature Cellular Senescence of Human Retinal Pigment Epithelium Cells and Reduces Ocular Disorders in Healthy Humans

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    Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy humans. First, we showed that KW3110 treatment of mouse macrophages (J774A.1) produced significantly higher levels of interleukin-10 as compared with other lactic acid bacterium strains (all p &lt; 0.01). Transferring supernatant from KW3110- and E. coli 0111:B4 strain and adenosine 5&prime;-triphosphate (LPS/ATP)-stimulated J774A.1 cells to human retinal pigment epithelium (ARPE-19) cells suppressed senescence-associated phenotypes, including proliferation arrest, abnormal appearance, cell cycle arrest, and upregulation of cytokines, and also suppressed expression of tight junction molecule claudin-1. A randomized, double-blind, placebo-controlled parallel-group study of healthy subjects (n = 88; 35 to below 50 years) ingesting placebo or KW3110-containing supplements for 8 weeks showed that changes in critical flicker frequency, an indicator of eye fatigue, from the week-0 value were significantly larger in the KW3110 group at weeks 4 (p = 0.040) and 8 (p = 0.036). These results suggest that KW3110 protects ARPE-19 cells against premature senescence and aberrant expression of tight junction molecules caused by chronic inflammatory stress, and may improve chronic eye disorders including eye fatigue

    Lung histopathology of mPIV1-infected mice.

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    <p>A. Representative hematoxylin and eosin (H & E)-stained sections of lung tissues from control and JCM5805 group mice (6 mice per group). Lung tissues were prepared from mice 3 days after infection. Scale bars, 300 μm. B. Histological scoring of lung tissues from mPIV1-infected mice belong to control (open columns) and JCM5805 (dot columns) group. Sections were scored at four levels as follows: 0, no symptoms; 1, low pathogenicity; 2, medium pathogenicity; 3, high pathogenicity. The mean ± SD of the tissues in each group is shown. *<i>P</i><0.05, **<i>P</i><0.01 (Mann-Whitney U test). The data shown is representative of two independent experiments.</p
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