Lactobacillus sakei WIKIM30 is a Gram-positive facultative anaerobic bacterium isolated from kimchi, a Korean fermented vegetable food. In this study, we found that WIKIM30 promoted regulatory T cell (Treg) differentiation by inducing dendritic cells with tolerogenic properties. The production of the T helper (Th) 2-associated cytokine interleukin (IL)-4 was decreased, but that of the Treg-associated cytokine IL-10 was increased in splenocytes from ovalbumin-sensitized mice treated with WIKIM30. We also investigated the inhibitory capacity of WIKIM30 on the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD), a Th2-dominant allergic disease in mice. Oral administration of L. sakei WIKIM30 significantly reduced AD-like skin lesions and serum immunoglobulin E and IL-4 levels while decreasing the number of CD4+ T cells and B cells and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in peripheral lymph nodes and enhancing Treg differentiation and IL-10 secretion in mesenteric lymph nodes. In addition, WIKIM30 modulated gut microbiome profiles that were altered in AD mice, which showed increases in Arthromitus and Ralstonia and a decrease in Ruminococcus abundance. These changes were reversed by WIKIM30 treatment. Notably, the increase in Ruminococcus was highly correlated with Treg-related responses and may contribute to the alleviation of AD responses. Together, these results suggest that oral administration of L. sakei WIKIM30 modulates allergic Th2 responses enhancing Treg generation and increases the relative abundance of intestinal bacteria that are positively related to Treg generation, and therefore has therapeutic potential for the treatment of AD.
Kimchi is a traditional Korean vegetable product that is naturally fermented by various microorganisms present in the raw materials. Among these microorganisms, lactic acid bacteria dominate the fermentation process. Natural fermentation with unsterilized raw materials leads to the growth of various lactic acid bacteria, resulting in variations in the taste and quality of kimchi, which may make it difficult to produce industrial-scale kimchi with consistent quality. The use of starter cultures has been considered as an alternative for the industrial production of standardized kimchi, and recent trends suggest that the demand for starter cultures is on the rise. However, several factors should be carefully considered for the successful application of starter cultures for kimchi fermentation. In this review, we summarize recent studies on kimchi starter cultures, describe practical problems in the application of industrial-scale kimchi production, and discuss the directions for further studies.
Mesenchymal stromal/stem cells (MSCs) have been developed as a promising source for cell-based therapies of ischemic disease. However, there are some hurdles in their clinical application such as poor cell engraftment and inconsistent stem cell potency. In this study, we sought to find biomarkers for predicting potency of MSCs for proangiogenic therapy to improve their beneficial effects. Large variations were observed in proangiogenic factor secretion profiles of conditioned media derived from nine different donor-derived Wharton's jelly (WJ)-derived MSCs and 8 factors among 55 angiogenesis-related factors were secreted at considerable levels. Two distinct WJ-MSCs that had the lowest or the highest secretion of these eight factors showed corresponding proangiogenic activities in in vitro angiogenesis assays. When four additional different donor-derived WJ-MSCs were further examined, proangiogenic activities in migration and tube formation of endothelial cells and in in vivo Matrigel plug assay were highly consistent with secretion levels of four major factors (angiogenin, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor). Such correlation was also observed in vascular regenerative effect in a mouse hind limb ischemia model. Blocking of these four factors by neutralizing antibodies or knockdown of them by siRNA treatment resulted in significant inhibition of proangiogenic activities of not only WJ-MSCs, but also bone marrow-derived MSCs. These results suggest that these four factors may represent efficient biomarkers for predicting vascular regenerative efficacy of MSCs. STEM CELLS 2019; 37:77-88 SIGNIFICANCE STATEMENTMesenchymal stromal/stem cells (MSCs) have been used for treatment of ischemic diseases. However, their inconsistent potency due to donor or source variation and culture condition has been a problem in clinical application. To find biomarkers of MSCs for predicting vascular regenerative potency, this study aimed to find correlations of secretion profile of paracrine factors with in vitro and in vivo proangiogenic activities. Four major factors (angiogenin, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor) were found to be efficient biomarkers for predicting vascular regenerative efficacy in the treatment of ischemic diseases.
IL1b is a central regulator of systemic inflammatory response in breast cancer, but the precise regulatory mechanisms that dictate the overproduction of IL1b are largely unsolved. Here, we show that IL1b secretion is increased by the coculture of human monocyte-like cells and triple-negative breast cancer (TNBC) cells. In addition, macrophages robustly produced IL1b when exposed to the conditioned media of TNBC cells. Consistent with these observations, macrophage depletion decreased serum IL1b and reduced breast cancer progression in an orthotopic breast cancer mouse model. Profiling the secretome of human breast cancer cells revealed that the CD44 antigen was the most differentially released protein in basal conditions of TNBC cells. Antibody-mediated neutralization of CD44 abrogated IL1b production in macrophages and inhibited the growth of primary tumors. These results suggest IL1b-mediated oncogenic signaling is triggered by breast cancer cell membrane-derived soluble CD44 (sCD44) antigen, and targeting sCD44 antigen may provide an alternative therapeutic strategy for breast cancer treatment by modulating inflammatory tumor microenvironment.Significance: A novel positive feedback loop between IL1b and CD44 promotes TNBC malignant progression.
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