Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Immunol ; 12: 650176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512619

RESUMO

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.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Complicações do Diabetes/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Pantoea/química , Administração Oral , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Células Cultivadas , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Transdução de Sinais
2.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34328201

RESUMO

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.


Assuntos
Morte Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Neurônios/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Receptores dos Hormônios Gastrointestinais/genética , Estreptozocina/farmacologia , Proteína bcl-X/genética
3.
Anticancer Res ; 41(8): 4053-4059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281874

RESUMO

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.


Assuntos
Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Quimiocina CCL7/genética , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Proteínas de Choque Térmico HSP40/genética , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia
4.
Anticancer Res ; 40(8): 4457-4464, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727775

RESUMO

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.


Assuntos
Arginase/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Lipopolissacarídeos/efeitos adversos , Macrófagos Peritoneais/fisiologia , Receptores de Formil Peptídeo/genética , Receptores dos Hormônios Gastrointestinais/genética , Administração Oral , Animais , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Especificidade de Órgãos , Fagocitose/efeitos dos fármacos , Fenótipo , Cultura Primária de Células , Regulação para Cima
5.
Anticancer Res ; 40(8): 4681-4685, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727792

RESUMO

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.


Assuntos
Elastina/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ácido Hialurônico/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Linhagem Celular , Humanos , Ativação de Macrófagos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pantoea/metabolismo , Fagocitose/efeitos dos fármacos , Células Th1
6.
Anticancer Res ; 40(8): 4711-4717, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727797

RESUMO

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.


Assuntos
Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Animais , Linhagem Celular , Citocinas/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
7.
Sci Rep ; 10(1): 8945, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488176

RESUMO

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.


Assuntos
Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fenótipo , Transdução de Sinais/efeitos dos fármacos
8.
J Appl Toxicol ; 40(10): 1342-1352, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32346895

RESUMO

Pantoea agglomerans is a Gram-negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide-containing fermented wheat flour extract from P. agglomerans (Somacy-FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with Somacy-FP100 reported its lack of genotoxicity in vitro, but a subchronic toxicity study has not yet been performed. Therefore, to demonstrate the safety of Somacy-FP100 for use as a food ingredient, a 90-day oral (gavage) toxicity study in rats was conducted. Male and female Han Wistar rats were administered vehicle (control) or Somacy-FP100 at 500, 1500, or 4500 mg/kg body weight/day at a dose volume of 10 mL/kg body weight, for at least 90 days. No test article-related adverse clinical signs or effects on body weight, food consumption, or clinical pathology were observed, and there were no macroscopic or microscopic findings related to the test article. Therefore, 4500 mg/kg body weight/day (the highest dose tested and highest feasible dose) was established as the no-observed-adverse-effect level. This absence of subchronic toxicity, in addition to the previously reported lack of genotoxicity, demonstrates the safety of Somacy-FP100 for use as a food ingredient.

9.
In Vivo ; 33(1): 109-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587610

RESUMO

BACKGROUND/AIM: Recently, the prevalence of atopic dermatitis (AD) has increased in developed countries. This study aimed to examine the usefulness of a moisturizing cream containing lipopolysaccharide derived from Pantoea agglomerans (LPSp) in patients with mild AD. PATIENTS AND METHODS: A moisturizing cream containing LPSp or its placebo was randomly assigned and continuously used for 4 weeks in patients with mild AD. AD severity was evaluated in a double-blind manner by a dermatologist using the Eczema Area and Severity Index (EASI) score and by the patients' self-evaluation of itching and skin condition using a visual analog scale (VAS). RESULTS: Although there was no difference in the EASI score between the two groups, the VAS scores showed significantly greater symptom alleviation in the LPSp group than in the placebo group. CONCLUSION: A moisturizing cream containing LPSp may be effective for routine skin care and could help alleviate symptoms of mild AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Higiene da Pele/métodos , Adulto , Dermatite Atópica/imunologia , Dermatite Atópica/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Creme para a Pele/administração & dosagem , Resultado do Tratamento
10.
Anticancer Res ; 38(7): 4339-4345, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970571

RESUMO

BACKGROUND/AIM: Dewaxed brown rice has macrophage activation ability via TLR4 and contains a high amount of lipopolysaccharides (LPS). It is expected that dewaxed brown rice can help prevent lifestyle diseases. In this study, the anti-obesity effect of dewaxed brown rice was investigated using obese and diabetic model mice. MATERIALS AND METHODS: Dewaxed brown rice and white rice were polished and powdered by Toyo Rice Co. Diet pellets were prepared (AIN-93) with 50% dewaxed brown rice or white rice powder and fed to type II diabetic model KK-Ay mice for 10 weeks. Weight and fasting blood glucose were measured every week, and whole blood and liver was collected on the final day for the evaluation of biochemical data. RESULTS: A 20% reduction in body weight was found in the dewaxed brown rice feed and white rice feed groups compared to the normal feed group. Fasting blood glucose increased in the normal-diet group, but on the other hand, the blood glucose in the white rice and the dewaxed brown rice feed group was almost constant. Dewaxed brown rice feed group of plasma ALT and AST, liver TG and T-CHO were significantly lower than that of the control and the white rice feed group. CONCLUSION: Dewaxed brown rice feed has an anti-obesity effect to suppress increasing body weight, fasting blood glucose, and an effect of suppressing fatty liver.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Obesidade , Oryza , Animais , Dieta , Modelos Animais de Doenças , Feminino , Manipulação de Alimentos/métodos , Camundongos , Oryza/química
11.
PLoS One ; 13(6): e0198493, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29856882

RESUMO

The pathogenesis of Alzheimer's disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-ß (Aß) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aß clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aß clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aß phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aß burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aß phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.


Assuntos
Doença de Alzheimer/patologia , Dieta Hiperlipídica , Lipopolissacarídeos/uso terapêutico , Transtornos da Memória/prevenção & controle , Doenças Metabólicas/prevenção & controle , Pantoea/metabolismo , Administração Oral , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Glucose/metabolismo , Hemoglobina A Glicada/análise , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Doenças Metabólicas/patologia , Camundongos , Microglia/citologia , Microglia/metabolismo , Fagocitose
12.
PLoS One ; 13(3): e0195008, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29584779

RESUMO

Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or sublingual administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.


Assuntos
Apolipoproteínas E/genética , Dieta Hiperlipídica , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pantoea/metabolismo , Placa Aterosclerótica/prevenção & controle , Administração Oral , Animais , Apolipoproteínas E/deficiência , Peso Corporal/efeitos dos fármacos , Quimiocina CCL2/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/prevenção & controle , Interleucina-6/análise , Interleucina-6/sangue , Intestinos/microbiologia , Lipopolissacarídeos/administração & dosagem , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Placa Aterosclerótica/etiologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue
13.
Food Sci Nutr ; 6(1): 197-206, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29387379

RESUMO

In this study, the effects on the maintenance of normal bloodstream by lipopolysaccharide (LPS) were investigated in the parallel-group randomized double-blind study using supplement containing Pantoea agglomerans LPS (201.5 µg/tablet as LPS). Screening was previously performed in the implementation of the study. Adult males and females with normal value to borderline (healthy subjects) in the hematologic parameters, for which reference values were given, were chosen in this study. The period of ingestion of the supplement was 3 months. As the result, a significant decrease in the rate of change (the ratio when the baseline was 1) of HbA1c, which is a glycative stress marker, was found in the group which ingested LPS supplement after 3 months. Also, a significant increase in the number of fingertip capillary vessels was found compared with the control group. From these results, the effects of the maintenance of bloodstream by ingestion of LPS were shown.

14.
Anticancer Res ; 37(7): 3917-3920, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668895

RESUMO

BACKGROUND/AIM: Recent studies reported that lipopolysaccharide (LPS) exhibits beneficial effects on prevention of immune-related diseases by activating macrophages. We previously demonstrated that pre-treatment with LPS derived from Pantoea agglomerans (LPSp) activated amyloid ß (Aß) phagocytosis in mouse primary microglia. In the present study, we further examined the promotory effect on phagocytosis of phagocytic particles in the C8-B4 microglia cell line. MATERIALS AND METHODS: Phagocytic analysis of C8-B4 cells was evaluated using phagocytic particles (latex beads or HiLyte™ Fluor 488-conjugated Aß1-42). RESULTS: The phagocytic activity of latex beads was dependent on the concentration of beads and incubation time. LPSp, at as low as 100 pg/ml, significantly increased phagocytosis against the beads. In the experiment of Aß1-42 phagocytosis, LPSp significantly increased Aß phagocytic activity. CONCLUSION: LPSp treatment was confirmed to enhance Aß1-42 phagocytosis by mouse microglia. It is suggested that the use of LPSp may be a potential promising candidate for the prevention of Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Pantoea/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Microglia/metabolismo , Fagocitose
15.
In Vivo ; 31(4): 573-577, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652422

RESUMO

BACKGROUND/AIM: A decrease in gastrointestinal motility causing weakened lipopolysaccharide (LPS) - toll-like receptor (TLR)4 signaling along with a decline in the number of enteric bacteria is known to be a cause of constipation due to the administration of antibiotics. A new type of brown rice with its wax layer removed, resulting in quick-cooking and tasty product, contains 100-times more LPS than polished white rice. In this study, the improvement effect on constipation due to intake of dewaxed brown rice was examined. MATERIALS AND METHODS: Dewaxed brown rice was prepared at Toyo Rice from brown rice. Mice were given powdered feed to which powdered rice containing 0-50% of dewaxed brown rice was added. Antibiotics were administered for 10 or 27 days in drinking water containing vancomycin, metronidazole and neomycin. LPS, used as a control, was freely provided in drinking water. The defecation frequency, stool weight per hour and body weight were determined on the last day. RESULTS: Although the 10-day administration of antibiotics reduced the stool weight per hour to half, the dewaxed brown rice and LPS groups showed a trend towards improvement at a level comparable to the group receiving no antibiotics. The body weight significantly decreased after the 27-day administration of antibiotics but was improved in the 50% dewaxed brown rice group at a level comparable to the group receiving no antibiotics. Though the defecation frequency and wet and dry stool weights per hour were reduced by as much as 50% in the group receiving antibiotics, a significant improvement in constipation was observed in the 50% dewaxed brown rice group. CONCLUSION: As the improvement effect of dewaxed brown rice on body weight loss and constipation caused by the long-term administration of antibiotics has been confirmed in animal experimentation, the introduction of dewaxed brown rice as a staple food to patients under long-term antibiotic treatment may improve constipation.


Assuntos
Antibacterianos/administração & dosagem , Constipação Intestinal/dietoterapia , Gastroenteropatias/dietoterapia , Animais , Peso Corporal , Constipação Intestinal/fisiopatologia , Fezes , Gastroenteropatias/fisiopatologia , Humanos , Camundongos , Oryza/química , Receptor 4 Toll-Like , Vancomicina/administração & dosagem
16.
Anticancer Res ; 36(7): 3599-605, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27354629

RESUMO

BACKGROUND/AIM: Oral ingestion of lipopolysaccharide (LPS) has been shown to be effective in diseases' prevention. Brown rice contains large amounts of LPS not actively consumed because of bad taste. Recently, a new type of brown rice with its wax layer removed has been produced. In this report, we measured the LPS content of this dewaxed rice and evaluated the function of innate immune activation on macrophages. MATERIALS AND METHODS: Dewaxed brown rice and polished rice were prepared using the Saika-style rice polishing process. LPS content extracted using hot water from this sample was evaluated by the Limulus reaction and the activation of macrophage RAW246.7 cells was evaluated by nitric oxide (NO) production. In addition, toll-like receptors (TLRs) 2-, 4- and 9-induced human embryonic kidney (HEK) 293 cells were used for the confirmation of the activated pathway. RESULTS: Mean LPS content in the 15 types of dewaxed brown rice was found to be 6.4±2.6 µg/g, while that of brown rice was 10.9±4.3 µg/g. The extract of dewaxed brown rice induced significant amounts of NO by RAW246.7 cells, while production was reduced to 1/6 by adding polymyxin B. The macrophage activating effect of dewaxed brown rice was 79- and 51-times higher than that of polished rice in TLR4- and 2-induced HEK 293 cells. CONCLUSION: LPS content in dewaxed brown rice was found to be able to activate macrophages. This rice activated macrophages mainly via the TLR4 and, to a lesser extent, TLR2 pathways. It is suggested that dewaxed brown rice can be considered effective in allergy and cancer prevention.


Assuntos
Anticarcinógenos/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Oryza/química , Receptor 4 Toll-Like/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Ifosfamida , Imunidade Inata , Camundongos , Mitomicina , Óxido Nítrico/metabolismo , Células RAW 264.7 , Ceras/química
17.
Anticancer Res ; 36(7): 3687-92, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27354641

RESUMO

BACKGROUND/AIM: The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. MATERIALS AND METHODS: The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 µg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. RESULTS: IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). CONCLUSION: An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine.


Assuntos
Adjuvantes Imunológicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Lipopolissacarídeos/farmacologia , Animais , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Células Epidérmicas , Epiderme/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Masculino , Camundongos Endogâmicos C3H , Pessoa de Meia-Idade , Pantoea/química
18.
Anticancer Res ; 36(7): 3693-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27354642

RESUMO

BACKGROUND/AIM: Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll-like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid ß (Aß) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Aß phagocytosis in microglia is still unknown. MATERIALS AND METHODS: Primary microglial cells were isolated from adult mouse brain by enzymatic digestion, following myelin removal and magnetic separation of cluster of differentiation (CD) 11b. Phagocytic analysis of the primary microglia was measured by using HiLyte™ Fluor 488-conjugated Aß1-42 RESULTS: Using our protocols, the average yield of isolated CD11b(+) cells was around 2.2×10(5) cells per brain. CD11b(+)CD45(+)CD39(+) cells were defined here as microglia. The phagocytic activity of Aß1-42 by the isolated microglia was confirmed. LPSp (10 ng/ml) pre-treatment for 18 h significantly increased Aß phagocytic activity. CONCLUSION: The enhancement of Aß1-42 phagocytosis by LPSp treatment in the primary mouse microglia was demonstrated for the first time.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/imunologia , Fragmentos de Peptídeos/metabolismo , Fagocitose/imunologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Sobrevivência Celular , Células Cultivadas , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Pantoea/química , Cultura Primária de Células
19.
In Vivo ; 30(3): 205-11, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27107076

RESUMO

BACKGROUND/AIM: Bacterial lipopolysaccharide (LPS) is involved in the activation of the innate immune responses on monocytes/macrophages in vitro, and by intravenous injection. Although small quantities of LPS are usually found in traditional Chinese medicines, vegetables and fruits, the mode of action of orally administered LPS is still unclear. MATERIALS AND METHODS: LPS derived from Pantoea agglomerans (LPSp) was orally administered to C3H/HeN or C3H/HeJ mice ad libitum. RESULTS: The LPSp treatment enhanced phagocytosis by resident peritoneal macrophages of C3H/HeN mice but not of C3H/HeJ mice. This activation can be defined as primed activation because no augmentation of inflammatory cytokines production was detected. LPSp in peritoneal fluid was detected and successfully quantified. Moreover, the LPSp reduced the expression of avian reticuloendotheliosis viral oncogene-related B (RelB) in the macrophages without degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (IκBα). CONCLUSION: Orally administered LPSp can reach the peritoneum, and enhance phagocytosis via Toll-like receptor 4 signaling pathway in resident peritoneal macrophages.


Assuntos
Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Pantoea/química , Administração Oral , Animais , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Citometria de Fluxo , Immunoblotting , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/imunologia , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos Endogâmicos C3H , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelB/imunologia , Fator de Transcrição RelB/metabolismo
20.
Anticancer Res ; 35(8): 4461-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26168487

RESUMO

BACKGROUND: Oral administration of lipopolysaccharide (LPS), a major outer-membrane component of Gram-negative bacteria, has been found to prevent infection in mammals and fish. Oral administration of LPS is believed to increase phagocytic activity and promote cytokine production, thus associating it with priming. The present study aimed to elucidate the effect of oral administration of LPS in birds, which phylogenetically lie between fish and mammals, using chickens as a model. MATERIALS AND METHODS: LPS derived from Pantoea agglomerans (LPSp) was added to the feed or water for oral administration to broiler chickens. For the survival assay and gene expression analysis (Genopal), LPSp was administered at a dose of 10 µg/kg of body weight (BW)/day. LPSp was administered at a dose of 0.2 µg/kg or 200 µg/kg to stimulate peripheral blood mononuclear phagocytosis (latex beads) and nitric oxide (NO) production. RESULTS: LPSp (10 µg/kg BW/day) administration significantly inhibited mortality in broiler chickens on commercial farms. Furthermore, oral administration resulted in a transient increase in phagocytic activity and improved the ability to produce NO. On examining splenic cytokine induction following intraperitoneal administration of LPS derived from Escherichia coli (LPSe), we found significantly increased interleukin (IL)-1ß mRNA expression. CONCLUSION: Innate immunity activation in chickens, as seen in infection prevention, was induced by oral administration of LPSp. This infection prevention involved increased phagocytic activity and enhanced gene expression and appears to be a phylogenetically-preserved innate immunity mechanism.


Assuntos
Infecções Bacterianas/imunologia , Galinhas/imunologia , Imunidade Inata/imunologia , Lipopolissacarídeos/administração & dosagem , Pantoea/imunologia , Administração Oral , Animais , Infecções Bacterianas/prevenção & controle , Citocinas/biossíntese , Citocinas/imunologia , Perfilação da Expressão Gênica , Interleucina-1beta/genética , Macrófagos/imunologia , Óxido Nítrico/biossíntese , Fagocitose/imunologia , RNA Mensageiro/biossíntese
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...