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1.
Sci Rep ; 14(1): 15394, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965275

ABSTRACT

Some herbal extracts contain relatively high amounts of lipopolysaccharide (LPS). Because orally administered LPS activates innate immunity without inducing inflammation, it plays a role as an active ingredient in herbal extracts. However, the LPS content in herbal extracts remains extensively unevaluated. This study aimed to create a database of LPS content in herbal extracts; therefore, the LPS content of 414 herbal extracts was measured and the macrophage activation potential was evaluated. The LPS content of these hot water extracts was determined using the kinetic-turbidimetric method. The LPS concentration ranged from a few ng/g to hundreds of µg/g (Standard Escherichia coli LPS equivalent). Twelve samples had a high-LPS-content of > 100 µg/g, including seven samples from roots and three samples from leaves of the herbal extracts. These samples showed high phagocytosis and NO production capacity, and further investigation using polymyxin B, an LPS inhibitor, significantly inhibited macrophage activation. This study suggests that some herbal extracts contain sufficient LPS concentration to activate innate immunity. Therefore, a new approach to evaluate the efficacy of herbal extracts based on their LPS content was proposed. A database listing the LPS content of different herbal extracts is essential for this approach.


Subject(s)
Immunity, Innate , Lipopolysaccharides , Macrophage Activation , Phagocytosis , Plant Extracts , Plant Extracts/pharmacology , Plant Extracts/chemistry , Immunity, Innate/drug effects , Phagocytosis/drug effects , Animals , Mice , Macrophage Activation/drug effects , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Nitric Oxide/metabolism , Plant Leaves/chemistry
2.
Vet Immunol Immunopathol ; 265: 110664, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37918120

ABSTRACT

This study aimed to evaluate the effect of orally administered lipopolysaccharide (LPS) derived from Pantoea agglomerans (LPSpa) on innate immune functions, including the concentrations of antimicrobial components and interleukin (IL)-10 in goat milk, for the prevention of goat mastitis. Twelve Tokara goats were divided into two groups of six goats. Goats in the LPSpa and control groups were orally administrated with 0.4 g/kg dextrin with or without 0.02 mg/kg LPSpa for 7 days (day 0-6), respectively. After treatment (i.e., day 7), 1 µg LPS from Escherichia coli O111 (LPSec) was infused into one side of the udder in both groups to induce mastitis. Milk from all sides of the udder, saliva, and feces were collected on days 0 and 7. After LPSec infusion into the udders, milk was collected from the infused side of the udder on days 8, 10, and 12. Milk yields and somatic cell counts were recorded during the examination period. The concentrations of immunoglobulin (Ig) A in saliva, feces, and milk and the concentrations of lactoferrin, goat ß defensin-1 (GBD1), S100A7, and IL-10 in milk were measured. After LPSpa oral administration, the concentrations of GBD-1 and IL-10 in the milk of the LPSpa group were significantly higher on day 7 than those in the control group, and the concentration of IgA in the feces tended to be higher than that in the control group. After LPSec intramammary infusion, S100A7 concentration on day 12 was significantly lower in the LPSpa group than in the control group. These findings suggest that the oral administration of LPSpa may prevent mastitis by increasing the concentration of GBD1 in milk.


Subject(s)
Goat Diseases , Mastitis , Pantoea , Female , Animals , Lipopolysaccharides/pharmacology , Interleukin-10 , Milk , Immunity, Innate , Administration, Oral , Escherichia coli , Goats , Mammary Glands, Animal , Mastitis/veterinary
3.
Int J Mol Sci ; 24(18)2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37762690

ABSTRACT

Lipopolysaccharide (LPS) is a bacterial component that activates intracellular signaling pathways upon binding to the Toll-like receptor (TLR)-4/MD-2 complex. It is well known that LPS injected into animals and high-dose (100 ng/mL to 1 µg/mL) LPS treatment to innate immune cells induce an inflammatory response. In contrast, LPS is naturally present in the gastrointestinal tract, respiratory tract, and skin of humans and animals, and it has been shown that TLR-4-deficient animals cannot maintain their immune balance and gut homeostasis. LPS from commensal bacteria can help maintain homeostasis against mucosal stimulation in healthy individuals. Oral LPS administration has been shown to be effective in preventing allergic and lifestyle-related diseases. However, this effect was not observed after treatment with LPS at high doses. In mice, oral LPS administration resulted in the detection of LPS at a low concentration in the peritoneal fluid. Therefore, LPS administered at low and high doses have different effects. Moreover, the results of in vitro experiments using low-dose LPS may reflect the effects of oral LPS administration. This review summarizes the utility of in vitro models using cells stimulated with LPS at low concentrations (50 pg/mL to 50 ng/mL) in elucidating the mechanisms of oral LPS administration. Low-dose LPS administration has been demonstrated to suppress the upregulation of proinflammatory cytokines and promote wound healing, suggesting that LPS is a potential agent that can be used for the treatment and prevention of lifestyle-related diseases.


Subject(s)
Lipopolysaccharides , Wound Healing , Humans , Animals , Mice , Lipopolysaccharides/toxicity , Skin , Anti-Inflammatory Agents , Administration, Oral
4.
Int J Mol Sci ; 24(5)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36902049

ABSTRACT

Lipopolysaccharide (LPS), an endotoxin, induces systemic inflammation by injection and is thought to be a causative agent of chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). However, our previous studies found that oral LPS administration does not exacerbate T2DM conditions in KK/Ay mice, which is the opposite of the response from LPS injection. Therefore, this study aims to confirm that oral LPS administration does not aggravate T2DM and to investigate the possible mechanisms. In this study, KK/Ay mice with T2DM were orally administered LPS (1 mg/kg BW/day) for 8 weeks, and blood glucose parameters before and after oral administration were compared. Abnormal glucose tolerance, insulin resistance progression, and progression of T2DM symptoms were suppressed by oral LPS administration. Furthermore, the expressions of factors involved in insulin signaling, such as insulin receptor, insulin receptor substrate 1, thymoma viral proto-oncogene, and glucose transporter type 4, were upregulated in the adipose tissues of KK/Ay mice, where this effect was observed. For the first time, oral LPS administration induces the expression of adiponectin in adipose tissues, which is involved in the increased expression of these molecules. Briefly, oral LPS administration may prevent T2DM by inducing an increase in the expressions of insulin signaling-related factors based on adiponectin production in adipose tissues.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Lipopolysaccharides , Animals , Mice , Adiponectin/metabolism , Administration, Oral , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/therapy , Insulin/metabolism , Insulin Resistance/physiology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/pharmacology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/therapy
5.
Anticancer Res ; 42(8): 3983-3991, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35896255

ABSTRACT

BACKGROUND/AIM: Lipopolysaccharide (LPS) is thought to be a causative agent of type 2 diabetes, because it has been shown that a single LPS stimulation in vitro induces chronic inflammation and reduces insulin signaling in adipocytes. However, oral LPS administration prevents type 2 diabetes, and this effect does not correspond to a single LPS adipocyte stimulation. In this study, the response of adipocytes to single and repeated stimulation with LPS was examined. MATERIALS AND METHODS: 3T3-L1 cells were differentiated into adipocytes and stimulated with LPS once or thrice every 24 h. The expression levels of inflammatory and anti-inflammatory factors and insulin sensitivity-related factors were measured. RESULTS: Single stimulation with LPS increased the mRNA and protein expression of inflammatory factors (interleukin-6 and monocyte chemotactic protein 1), but this increase was inhibited by repeated stimulation. In contrast, the mRNA expression levels of anti-inflammatory factors (proliferator-activated receptor γ and peroxisome proliferator-activated receptor gamma coactivator1 α) were increased by repeated LPS stimulation. Additionally, the mRNA expression levels of insulin sensitivity-related factors (glucose transporter type 4, insulin receptor, insulin receptor substrate 1 and thymoma viral proto-oncogene 2) in adipocytes were increased upon repeated LPS stimulation. CONCLUSION: Repetitive LPS stimulation, unlike single stimulation of adipocytes, upregulates anti-inflammatory and insulin signaling-related factors.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , 3T3-L1 Cells , Adipocytes/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Insulin/pharmacology , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Phenotype , RNA, Messenger/genetics
6.
Anticancer Res ; 42(8): 4049-4054, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35896268

ABSTRACT

BACKGROUND/AIM: Vascular endothelial cells play an important role in regulating immune responses and in keeping the balance between blood coagulation and fibrinolysis. Inflammatory cytokines produced by activated macrophages and vascular endothelial cells excessively activate vascular endothelial cells, leading to an imbalance in the expression of blood coagulation- and fibrinolysis-related factors. The dysfunction of vascular endothelial cells can lead to development of various diseases. In a previous study the increased expression of inflammatory cytokines in adipocytes was shown to be suppressed by the culture medium of macrophages activated by low-dose lipopolysaccharide (LPS). Suppressing inflammatory cytokine gene expression of low-dose LPS-activated macrophages may allow for the regulation of the dysfunction in vascular endothelial cells. MATERIALS AND METHODS: Human monocytes THP-1 cells were differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and were activated with LPS. The culture medium of the LPS-activated THP-1 was added to human aortic endothelial cells (HAoEC). After five days, the expression of inflammatory cytokine genes interleukin (IL)1B, IL6, IL8, and tumor necrosis factor (TNF)A, blood coagulation-related genes SERPINE1, tissue factor (TF), and thrombopoietin (TM), and fibrinolysis-related gene tissue-type plasminogen activator (t-PA) was analyzed using quantitative real-time PCR. RESULTS: IL1B, IL8, SERPINE1, TF, and TM expression in HAoEC was significantly reduced in the culture medium of super-low dose (0.1 ng/ml) LPS-activated macrophages. CONCLUSION: Super-low dose LPS-activated macrophages can suppress vascular endothelial cell inflammation and may be useful in preventing various diseases caused by the dysfunction of activated vascular endothelial cells.


Subject(s)
Cytokines , Lipopolysaccharides , Cytokines/genetics , Cytokines/metabolism , Endothelial Cells/metabolism , Humans , Interleukin-8/genetics , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Tetradecanoylphorbol Acetate , Tumor Necrosis Factor-alpha/metabolism
7.
Biochem Biophys Res Commun ; 586: 100-106, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34837833

ABSTRACT

Lipopolysaccharide (LPS) is the principal component of the outer membrane of gram-negative bacteria. The prior oral administration of LPS attenuates inflammatory responses, such as intestinal injury and atopic dermatitis, in mouse models; however, the underlying mechanism remains unclear. Here, we examined the effect of topical LPS application on allergic contact dermatitis and its mechanism of action using a murine contact hypersensitivity (CHS) model. Prolonged LPS application to the skin significantly suppressed 2,4-dinitrofluorobenzene (DNFB)-induced CHS. LPS application to the skin also reduced the phagocytosis of fluorescein isothiocyanate (FITC)-dextran by Langerhans and dendritic cells. Cutaneous cell migration into the skin-draining lymph nodes (LNs) induced by FITC painting was reduced by LPS application. During the CHS response, DNFB application induced T-cell proliferation and inflammatory cytokine production in skin-draining LNs, whereas prolonged LPS application inhibited DNFB-induced T-cell growth and interferon gamma production, indicating suppression of DNFB-induced sensitization. These results suggest that prolonged LPS application suppressed DNFB-induced sensitization and subsequently CHS response. Our findings imply that topical application of LPS may prevent allergic dermatitis such as CHS.


Subject(s)
Dermatitis, Contact/drug therapy , Immunologic Factors/pharmacology , Lipopolysaccharides/pharmacology , Lymphocytes/drug effects , Skin/drug effects , Administration, Cutaneous , Animals , Cell Line , Cell Movement/drug effects , Dendritic Cells/cytology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dermatitis, Contact/etiology , Dermatitis, Contact/immunology , Dermatitis, Contact/pathology , Dextrans/metabolism , Dinitrofluorobenzene/administration & dosage , Ear , Fluorescein-5-isothiocyanate/analogs & derivatives , Fluorescein-5-isothiocyanate/metabolism , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/immunology , Langerhans Cells/cytology , Langerhans Cells/drug effects , Langerhans Cells/immunology , Lymph Nodes/cytology , Lymph Nodes/drug effects , Lymph Nodes/immunology , Lymphocyte Activation/drug effects , Lymphocytes/cytology , Lymphocytes/immunology , Mice , Mice, Inbred C57BL , Phagocytosis/drug effects , Primary Cell Culture , Skin/immunology , Skin/pathology
8.
Front Immunol ; 12: 650176, 2021.
Article in English | MEDLINE | ID: mdl-34512619

ABSTRACT

Diabetes-related cognitive dysfunction (DRCD) is a serious complication induced by diabetes. However, there are currently no specific remedies for DRCD. Here, we show that streptozotocin-induced DRCD can be prevented without causing side effects through oral administration of lipopolysaccharide (LPS) derived from Pantoea agglomerans. Oral administration of LPS (OAL) prevented the cerebral cortex atrophy and tau phosphorylation induced by DRCD. Moreover, we observed that neuroprotective transformation of microglia (brain tissue-resident macrophages) is important for preventing DRCD through OAL. These findings are contrary to the general recognition of LPS as an inflammatory agent when injected systemically. Furthermore, our results strongly suggest that OAL promotes membrane-bound colony stimulating factor 1 (CSF1) expression on peripheral leukocytes, which activates the CSF1 receptor on microglia, leading to their transformation to the neuroprotective phenotype. Taken together, the present study indicates that controlling innate immune modulation through the simple and safe strategy of OAL can be an innovative prophylaxis for intractable neurological diseases such as DRCD. In a sense, for modern people living in an LPS-depleted environment, OAL is like a time machine that returns microglia to the good old LPS-abundant era.


Subject(s)
Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Diabetes Complications/drug therapy , Lipopolysaccharides/administration & dosage , Neuroprotective Agents/administration & dosage , Pantoea/chemistry , Administration, Oral , Animals , Brain/drug effects , Brain/metabolism , Brain/pathology , Cells, Cultured , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/prevention & control , Diabetes Mellitus, Experimental , Disease Models, Animal , Male , Mice , Microglia/drug effects , Microglia/metabolism , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Signal Transduction
9.
Anticancer Res ; 41(8): 4053-4059, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34281874

ABSTRACT

BACKGROUND/AIM: Diabetes is a risk factor for dementia. However, no radical preventive method for diabetes-associated dementia has yet been developed. Our previous study revealed that oral administration of lipopolysaccharide (LPS) prevents high-fat diet-induced cognitive impairment. Therefore, we investigated here whether oral administration of LPS (OAL) could also prevent diabetes-associated dementia. MATERIALS AND METHODS: Diabetic mice were produced by intraperitoneal administration of streptozotocin (STZ), and then mice were orally administered LPS. Cognitive ability was evaluated using the Morris water maze, and gene expression was analyzed in isolated microglia. RESULTS: OAL prevented STZ-induced diabetic cognitive impairment, but did not affect blood glucose levels. Moreover, OAL promoted the expression of neuroprotective genes in microglia, such as heat shock protein family 40 (HSP40) and chemokine CCL7. CONCLUSION: OAL prevents diabetes-associated dementia, potentially via promotion of HSP40 and CCL7 expression in microglia.


Subject(s)
Cognitive Dysfunction/prevention & control , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Lipopolysaccharides/therapeutic use , Neuroprotective Agents/therapeutic use , Administration, Oral , Animals , Blood Glucose/drug effects , Chemokine CCL7/genetics , Cognitive Dysfunction/blood , Cognitive Dysfunction/etiology , Cognitive Dysfunction/genetics , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/genetics , HSP40 Heat-Shock Proteins/genetics , Lipopolysaccharides/pharmacology , Male , Mice, Inbred C57BL , Microglia/drug effects , Microglia/metabolism , Neuroprotective Agents/pharmacology
10.
Anticancer Res ; 41(8): 4071-4076, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34281876

ABSTRACT

BACKGROUND/AIM: Increased expression of inflammatory cytokine genes through cell interactions in tissues may cause chronic inflammation, leading to the development of lifestyle-related diseases. Since the activation of inflammatory cytokine genes in monocytes/macrophages by co-culturing with cancer cells or adipocytes was suppressed by pre-treatment with low-dose lipopolysaccharide (LPS), we hypothesized that low-dose LPS-activated macrophages may regulate the expression of immune response-related genes in other cells. MATERIALS AND METHODS: Phorbol myristate acetate-treated human monocytes (THP-1) were activated by LPS. The conditioned medium of LPS-activated THP-1 cells was added to human adipocytes. After 5 days, the expression of genes encoding interleukin (IL)-6 (IL6), IL-8 (IL8), monocyte chemotactic protein (MCP)-1 (CCL2), adiponectin (ADIPOQ), and plasminogen activator inhibitor (PAI)-1 (SERPINE1) was analyzed using quantitative real-time PCR. RESULTS: The increased expression of inflammation-related genes and SERPINE1 in adipocytes was suppressed by the conditioned medium of THP-1 cells activated by low-dose LPS, whereas the expression of ADIPOQ was significantly increased. CONCLUSION: Low-dose LPS-activated macrophages convert adipocytes to anti-inflammatory phenotypes.


Subject(s)
Adipocytes/metabolism , Adiponectin/genetics , Cytokines/genetics , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Plasminogen Activator Inhibitor 1/genetics , Cell Line , Humans , Macrophage Activation
11.
Anticancer Res ; 41(8): 4093-4100, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34281880

ABSTRACT

BACKGROUND/AIM: We investigated the effect of Kumaizasa leaf extract (KLE) on innate immunity using the HEK293 and RAW 264.7 cell lines. MATERIALS AND METHODS: KLE, lipopolysaccharides (LPS), or KLE with LPS were added to RAW 264.7 cells. The TNF-α and IL-1ß mRNA expression was then quantified. The expression of MAPKs, NFĸB, TNF-α and IL-1ß proteins was also quantified. In addition, KLE was added to HEK293 cells and the IL-8 concentration was measured. RESULTS: In RAW 264.7 cells, KLE increased the levels of TNF-α and IL-1ß mRNA. By contrast, when KLE and LPS were added to RAW 264.7 cells, the increase in TNF-α and IL-1ß mRNA was ameliorated. Similarly, the expression of JNK and ERK proteins was reduced. The addition of KLE to HEK293 cells induced IL-8 production. CONCLUSION: Based on these results, a KLE-mediated mechanism may regulate immunity by suppressing the expression of JNK and ERK, which are involved in inflammatory signal transduction.


Subject(s)
Immunity, Innate/drug effects , Macrophages/drug effects , Plant Extracts/pharmacology , Sasa , Animals , Cytokines/genetics , Cytokines/immunology , Extracellular Signal-Regulated MAP Kinases/immunology , HEK293 Cells , Humans , JNK Mitogen-Activated Protein Kinases/immunology , Lipopolysaccharides/pharmacology , Macrophages/immunology , Mice , Plant Leaves , RAW 264.7 Cells
12.
Mol Med Rep ; 24(4)2021 Oct.
Article in English | MEDLINE | ID: mdl-34328201

ABSTRACT

Diabetes­associated neuronal dysfunction (DAND) is one of the serious complications of diabetes, but there is currently no remedy for it. Streptozotocin [2­deoxy­2­(3­methy1­3­nitrosoureido) D­glucopyranose; STZ] is one of the most well­established diabetes inducers and has been used in vivo and in vitro DAND models. The aim of the present study was to demonstrate that C8­B4 microglia transformed by the stimulus of repetitive low­dose lipopolysaccharide (LPSx3­microglia) prevent STZ­induced Neuro­2a neuronal cell death in vitro. The ELISA results showed that neurotrophin­4/5 (NT­4/5) secretion was promoted in LPSx3­microglia and the cell viability assay with trypan blue staining revealed that the culture supernatant of LPSx3­microglia prevented STZ­induced neuronal cell death. In addition, reverse transcription­quantitative PCR showed that neurons treated with the culture supernatant of LPSx3­microglia promoted the gene expression of B­cell lymphoma­extra large and glucose­dependent insulinotropic polypeptide receptor. Furthermore, the inhibition of tyrosine kinase receptor B, a receptor of NT­4/5, suppressed the neuroprotective effect of LPSx3­microglia. Taken together, the present study demonstrated that LPSx3­microglia prevent STZ­induced neuronal death and that NT­4/5 may be involved in the neuroprotective mechanism of LPSx3­microglia.


Subject(s)
Cell Death/drug effects , Lipopolysaccharides/pharmacology , Microglia/metabolism , Neurons/metabolism , Animals , Cell Line , Cell Survival/drug effects , Membrane Glycoproteins/antagonists & inhibitors , Mice , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Receptors, Gastrointestinal Hormone/genetics , Streptozocin/pharmacology , bcl-X Protein/genetics
13.
Anticancer Res ; 40(8): 4457-4464, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727775

ABSTRACT

BACKGROUND/AIM: Our previous studies suggested that oral administration of lipopolysaccharide (LPS) regulates the progression of various diseases via transformation of tissue-resident macrophages (MΦ). Recently, we characterized microglia transformed by repetitive low-dose LPS treatment (REPELL-microglia) in vitro, and this response was similar to that observed in response to oral administration of LPS in vivo. Here, we examined the characteristics of peritoneal tissue-resident MΦ (pMΦ) transformed by repetitive low-dose LPS treatment (REPELL-pMΦ). MATERIALS AND METHODS: Primary pMΦ were treated with low-dose LPS (1 ng/ml) three times; subsequently, phagocytic activity and gene expression were evaluated. RESULTS: REPELL-pMΦ exhibited high phagocytic activity and elevated expression of Arg1, Gipr, Gdnf, and Fpr2. The gene expression profiles observed in REPELL-pMΦ were distinct from those of REPELL-microglia. CONCLUSION: REPELL-pMΦ have the potential to promote clearance of xenobiotics and to suppress inflammation. The present study also demonstrates the diversity of tissue-resident MΦ transformation that reflect their tissue origin.


Subject(s)
Arginase/genetics , Glial Cell Line-Derived Neurotrophic Factor/genetics , Lipopolysaccharides/adverse effects , Macrophages, Peritoneal/physiology , Receptors, Formyl Peptide/genetics , Receptors, Gastrointestinal Hormone/genetics , Administration, Oral , Animals , Gene Expression Profiling/methods , Gene Expression Regulation/drug effects , Lipopolysaccharides/administration & dosage , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/drug effects , Male , Mice , Organ Specificity , Phagocytosis/drug effects , Phenotype , Primary Cell Culture , Up-Regulation
14.
Anticancer Res ; 40(8): 4681-4685, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727792

ABSTRACT

BACKGROUND/AIM: The functions of macrophages change in response to environmental factors such as lipopolysaccharide (LPS). LPS derived from Pantoea agglomerans (LPSp) is involved in macrophage activation and tissue repair when administered dermally. LPSp-activated macrophages may be useful for restoring and maintaining homeostasis of the skin. MATERIALS AND METHODS: Phorbol myristate acetate-treated human monocytes (THP-1 cells) were activated with LPSp. The medium of LPSp-activated THP-1 cells was added to normal human dermal fibroblasts (NHDF cells). After 24 h, the expression of hyaluronan (HA) synthase (HAS)2, hyaluronidase (HYAL)1, and tropoelastin in NHDF cells was analyzed using quantitative real-time PCR. RESULTS: The expression of HAS2 and tropoelastin was significantly increased, but that of HYAL1 was significantly decreased. It was demonstrated that the abilities of HA and elastin synthesis in NHDF cells increased through LPSp-activated THP-1 cells. CONCLUSION: LPSp-activated macrophages may be useful for enhancing the abilities of HA and elastin synthesis in fibroblasts, subsequently improving dysfunction and reducing various age-related disorders.


Subject(s)
Elastin/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Hyaluronic Acid/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Cell Line , Humans , Macrophage Activation , Monocytes/drug effects , Monocytes/metabolism , Pantoea/metabolism , Phagocytosis/drug effects , Th1 Cells
15.
Anticancer Res ; 40(8): 4711-4717, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727797

ABSTRACT

BACKGROUND: Continuous oral administration of lipopolysaccharide (LPS) enhances the phagocytic ability of macrophages, which is useful for preventing various diseases. Here, we attempted to create an in vitro model of continuous administration of LPS. MATERIALS AND METHODS: RAW264.7 cells were stimulated with LPS three times every 24 h (repeated stimulation), and phagocytic ability and inflammatory cytokine [interleukin-6 (IL6) and tumor necrosis factor-α (TNFα)] production were measured. RESULTS: The phagocytic ability was increased by a single stimulation with LPS and was maintained by repeated stimulation. IL6 production increased with a single stimulation with LPS; however, IL6 production by repeated stimulation with LPS was comparable to that of non-stimulation with LPS. On the other hand, the amount of TNFα was significantly increased by single and repeated stimulation with LPS. CONCLUSION: Repeated stimulation with LPS in RAW264.7 cells triggered a phenotype that was similar to that of macrophages after continuous oral administration of LPS. This suggests that this study model may reproduce the enhancement of macrophage phagocytosis, an effect afforded by continuous oral administration of LPS.


Subject(s)
Lipopolysaccharides/pharmacology , Macrophages/drug effects , Phagocytosis/drug effects , Animals , Cell Line , Cytokines/metabolism , Interleukin-6/metabolism , Macrophages/metabolism , Mice , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/metabolism
16.
Anticancer Res ; 40(8): 4719-4727, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727798

ABSTRACT

BACKGROUND/AIM: We investigated whether mastication affects microglia, whose activity is thought to be associated with cognition and brain tumor progression. MATERIALS AND METHODS: We kept mice by feeding either a hard or soft diet for 2, 4 or 8 months. After each period, we removed the whole brains and isolated microglia. The total RNA extracted from each brain's microglia was subjected to DNA microarray analysis. RESULTS: Many genes were found to be significantly differentially expressed between hard- and soft-diet-fed mice in each group of the same feeding period. The expression of several genes involved in the regulation of actin cytoskeleton was down-regulated in the soft-diet-fed mice. CONCLUSION: Mastication may affect microglia's roles in cognition as well as their neuroimmune activity through their activity of patrolling the brain.


Subject(s)
Mastication/physiology , Microglia/physiology , Transcriptome/physiology , Animals , Brain/physiology , Male , Mice , Mice, Inbred C3H
17.
Anticancer Res ; 40(8): 4755-4762, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727802

ABSTRACT

BACKGROUND: Developmental disorders are associated with microglial dysfunction. Oral administration of lipopolysaccharide derived from Pantoea agglomerans bacteria (LPSp) leads to normalization of phagocytic activity of microglia and suppression of inflammation in mice. In this article, we report on a successful trial in which we achieved a significant improvement of symptoms in patients with developmental disorders. PATIENTS AND METHODS: Five pediatric patients diagnosed with autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD) who visited our clinic received either 0.75 or 1 mg/day LPSp for 6 months or more, in addition to our usual therapy regimens (detoxification therapy, nutritional therapy, and vibration therapy). A survey questionnaire was completed by the patients' parents and evaluated using the Numerical Rating Scale. RESULTS: Behavior, verbal ability, and communication disabilities associated with ASD/ADHD improved in all patients. CONCLUSION: Oral administration of LPSp may represent a new treatment option in the area of developmental disorders where there is currently no treatment available.


Subject(s)
Developmental Disabilities/drug therapy , Lipopolysaccharides/administration & dosage , Pantoea/chemistry , Administration, Oral , Child , Child, Preschool , Cytokines/metabolism , Developmental Disabilities/metabolism , Female , Humans , Male , Microglia/drug effects , Microglia/metabolism , Phagocytosis/drug effects
18.
Sci Rep ; 10(1): 8945, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32488176

ABSTRACT

Although lipopolysaccharide (LPS) is regarded as an inducer of inflammation, previous studies have suggested that repetitive low-dose LPS has neuroprotective effects via immunomodulation of microglia, resident macrophages of brain. However, microglia transformed by the stimulus of repetitive low-dose LPS (REPELL-microglia) are not well characterized, whereas microglia transformed by repetitive high-dose LPS are well studied as an endotoxin tolerance model in which the induction of pro-inflammatory molecules is suppressed. In this study, to characterize REPELL-microglia, the gene expression and phagocytic activity of REPELL-microglia were analyzed with the murine C8-B4 microglia cell line. The REPELL-microglia were characterized by a high expression of pro-inflammatory molecules (Nos2, Ccl1, IL-12B, and CD86), anti-inflammatory molecules (IL-10, Arg1, Il13ra2, and Mrc1), and neuroprotective molecules (Ntf5, Ccl7, and Gipr). In addition, the phagocytic activity of REPELL-microglia was promoted as high as that of microglia transformed by single low-dose LPS. These results suggest the potential of REPELL-microglia for inflammatory regulation, neuroprotection, and phagocytic clearance. Moreover, this study revealed that gene expression of REPELL-microglia was distinct from that of microglia transformed by repetitive high-dose LPS treatment, suggesting the diversity of microglia transformation by different doses of LPS.


Subject(s)
Lipopolysaccharides/pharmacology , Microglia/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Cytokines/metabolism , Gene Expression/drug effects , Inflammation/metabolism , Lipopolysaccharides/metabolism , Macrophages/metabolism , Mice , Microglia/drug effects , Neuroprotection/drug effects , Neuroprotective Agents/pharmacology , Phenotype , Signal Transduction/drug effects
19.
Food Sci Nutr ; 7(11): 3520-3526, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31763002

ABSTRACT

Compared with regular brown rice, dewaxed brown rice (DBR), prepared by excluding only the wax layer in the outermost layer of brown rice using a new rice milling technique, has improved water absorbency, digestibility, and taste. Dewaxed brown rice has a nutritional value close to that of brown rice and contains a large amount of lipopolysaccharides (LPS), which are known to improve the cognitive function of mice. In this study, we examined the effect of continuous DBR ingestion on the cognitive function of elderly people. A crossover comparison test was performed, in which elderly people who moved into an elderly welfare facility were divided into two groups and ingested DBR or polished white rice for three meals a day for 6 months, followed by a change in test meals for the next 6 months. Cognitive function was assessed using Revised Hasegawa's Dementia Scale (HDS-R) before starting the test and 6 months after ingesting each test meal. No subjects withdrew or discontinued DBR intake during the study period, and all subjects continued the test for 6 months. In subjects with low cognitive function (defined as subjects with HDS-R total score of ≥1 but <10 at the start of the study), there was a significant association between continuous DBR ingestion and cognitive function improvement (increase in total HDS-R score). Our findings suggest that the long-term DBR ingestion as a staple food could be useful for preventing cognitive decline in elderly; it offers an easily implemented option as a daily diet for preventing cognitive decline.

20.
J Nutr Sci Vitaminol (Tokyo) ; 65(Supplement): S122-S124, 2019.
Article in English | MEDLINE | ID: mdl-31619610

ABSTRACT

Dewaxed brown rice (DBR), which is prepared by removing only the outermost wax layer of brown rice using a new rice milling technique, has improved water absorbency, digestibility, and taste compared to regular brown rice. DBR has a nutritional value close to that of brown rice, including a rich amount of lipopolysaccharides that are known to improve cognitive function in mice. This study thus aimed to verify the influence of continuous DBR ingestion on cognitive function among elderly individuals. The present study employed a crossover comparison design using the Revised Hasegawa Dementia Scale to assess cognitive function. Our findings confirmed that long-term DBR ingestion contributed to the prevention and reduction of overall cognitive decline, especially among elderly individuals with low cognitive function. Thus, DBR has the potential to be a useful staple food that maintains brain homeostasis among elderly individuals.


Subject(s)
Cognition/physiology , Cognitive Dysfunction/prevention & control , Diet/methods , Eating/physiology , Oryza/chemistry , Aged , Female , Humans , Male , Nutritive Value
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