Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
Add more filters











Publication year range
1.
Cell Rep ; 43(8): 114565, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39083380

ABSTRACT

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4+ T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-ß) plus IL-4 activates pSmad3-Ser213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-ß-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc.


Subject(s)
Interleukin-9 , MicroRNAs , Scleroderma, Systemic , MicroRNAs/metabolism , MicroRNAs/genetics , Animals , Scleroderma, Systemic/pathology , Scleroderma, Systemic/genetics , Scleroderma, Systemic/immunology , Humans , Mice , Interleukin-9/metabolism , Interleukin-9/genetics , Mice, Inbred C57BL , TNF Receptor-Associated Factor 6/metabolism , TNF Receptor-Associated Factor 6/genetics , Transforming Growth Factor beta/metabolism , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , Smad3 Protein/metabolism , Female , Interleukin-4/metabolism , Male , Bleomycin , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Signal Transduction
2.
Clin Psychopharmacol Neurosci ; 21(4): 758-768, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37859449

ABSTRACT

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

3.
Psychiatry Investig ; 20(6): 567-574, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37357672

ABSTRACT

OBJECTIVE: Previous studies have shown the influence of visual and auditory sensory impairment on dementia incidence. In this study, we tested the hypothesis that the incidence of dementia will increase with visual and auditory impairments than with visual or auditory impairment. METHODS: Data from the Korea National Health Insurance Service database were used, including disease and medication codes from 2009 to 2018, and the 2011 national health check-up results. Participants were grouped based on their sensory abilities: normal, visual impairment, auditory impairment, and both visual and auditory impairments (dual sensory impairment). To compare the incidence of dementia, hazard ratios were calculated for each group, with reference to the normal sensory (NS) group. Sensitivity analyses were performed comparing dementia incidence from 2014 to 2018, excluding the onset of the disease in 2012 and 2013. RESULTS: We identified 8,289 cases of dementia during the seven-year follow-up. In the multiple Cox regression analysis, adjusted for sex, social economic status, age, comorbidities, smoking, alcohol consumption, and activity level, the auditory impairment (hazard ratio= 1.1908) and visual impairment (hazard ratio=1.3553) groups showed a significantly higher dementia incidence than the NS group. Dual sensory impairment (hazard ratio=1.5267) showed the highest incidence. The sensitivity analysis yielded similar results. CONCLUSION: Visual and auditory impairments are associated with an increased risk of dementia, particularly in individuals with dual sensory impairment. Hence, visual and auditory impairments might have increased the risk of dementia through independent pathological processes. Therefore, preventing and correcting sensory impairment is necessary to reduce the risk of dementia.

4.
J Exp Bot ; 74(5): 1675-1689, 2023 03 13.
Article in English | MEDLINE | ID: mdl-36571808

ABSTRACT

Pathogen effectors can suppress various plant immune responses, suggesting that they have multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we screened the Phytophthora capsici RxLR cell death-inducer suppressing immune system (CRISIS). We found that the cell death induced by the CRISIS2 effector in Nicotiana benthamiana was inhibited by the irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin. Biochemical and gene-silencing analyses revealed that CRISIS2 physically and functionally associated with PMAs and induced host cell death independent of immune receptors. CRISIS2 induced apoplastic alkalization by suppressing PMA activity via its association with the C-terminal regulatory domain. In planta expression of CRISIS2 significantly enhanced the virulence of P. capsici, whereas host-induced gene-silencing of CRISIS2 compromised the disease symptoms and the biomass of the pathogen. Thus, our study has identified a novel RxLR effector that plays multiple roles in the suppression of plant defense and in the induction of cell death to support the pathogen hemibiotrophic life cycle in the host plant.


Subject(s)
Phytophthora infestans , Cell Death , Virulence , Nicotiana/genetics , Cell Membrane , Adenosine Triphosphatases , Plant Diseases , Plant Immunity/physiology
5.
Nat Commun ; 13(1): 6069, 2022 10 14.
Article in English | MEDLINE | ID: mdl-36241625

ABSTRACT

Interleukin-9 (IL-9)-producing CD4+ T helper cells (Th9) have been implicated in allergy/asthma and anti-tumor immunity, yet molecular insights on their differentiation from activated T cells, driven by IL-4 and transforming growth factor-beta (TGF-ß), is still lacking. Here we show opposing functions of two transcription factors, D-binding protein (DBP) and E2F8, in controlling Th9 differentiation. Specifically, TGF-ß and IL-4 signaling induces phosphorylation of the serine 213 site in the linker region of the Smad3 (pSmad3L-Ser213) via phosphorylated p38, which is necessary and sufficient for Il9 gene transcription. We identify DBP and E2F8 as an activator and repressor, respectively, for Il9 transcription by pSmad3L-Ser213. Notably, Th9 cells with siRNA-mediated knockdown for Dbp or E2f8 promote and suppress tumor growth, respectively, in mouse tumor models. Importantly, DBP and E2F8 also exhibit opposing functions in regulating human TH9 differentiation in vitro. Thus, our data uncover a molecular mechanism of Smad3 linker region-mediated, opposing functions of DBP and E2F8 in Th9 differentiation.


Subject(s)
Interleukin-4 , Interleukin-9 , Animals , Humans , Mice , Cell Differentiation/genetics , Interleukin-4/metabolism , Repressor Proteins/genetics , RNA, Small Interfering/metabolism , Serine/metabolism , T-Lymphocytes, Helper-Inducer , Transforming Growth Factor beta/metabolism , Transforming Growth Factors/metabolism
6.
Int J Mol Sci ; 23(15)2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35955819

ABSTRACT

The skin acts as a mechanical barrier that protects the body from the exterior environment, and skin barrier function is attributed to the stratum corneum (SC), which is composed of keratinocytes and skin lipids. Skin barrier homeostasis is maintained by a delicate balance between the differentiation and exfoliation of keratinocytes, and keratinocyte desquamation is regulated by members of the serine protease kalikrein (KLK) family and their endogenous inhibitor SPINK5/LEKTI (serine protease inhibitor Kazal type 5/lympho-epithelial Kazal-type-related inhibitor). Furthermore, SPINK5/LEKTI deficiency is involved in impaired skin barrier function caused by KLK over-activation. We sought to determine whether increased SPINK5/LEKTI expression ameliorates atopic dermatitis (AD) by strengthening skin barrier function using the ethanol extract of Lobelia chinensis (LCE) and its active compound, diosmetin, by treating human keratinocytes with UVB and using a DNCB-induced murine model of atopic dermatitis. LCE or diosmetin dose-dependently increased the transcriptional activation of SPINK5 promoter and prevented DNCB-induced skin barrier damage by modulating events downstream of SPINK5, that is, KLK, PAR2 (protease activated receptor 2), and TSLP (thymic stromal lymphopoietin). LCE or diosmetin normalized immune response in DNCB treated SKH-1 hairless mice as determined by reductions in serum immunoglobulin E and interleukin-4 levels and numbers of lesion-infiltrating mast cells. Our results suggest that LCE and diosmetin are good candidates for the treatment of skin barrier-disrupting diseases such as Netherton syndrome or AD, and that they do so by regulating SPINK5/LEKTI.


Subject(s)
Dermatitis, Atopic , Lobelia , Serine Peptidase Inhibitor Kazal-Type 5/metabolism , Animals , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Dinitrochlorobenzene , Flavonoids , Humans , Lobelia/metabolism , Mice , Proteinase Inhibitory Proteins, Secretory/pharmacology
7.
Biomol Ther (Seoul) ; 28(6): 542-548, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32938818

ABSTRACT

Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diosmetin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.

8.
J Immunol Res ; 2019: 3486841, 2019.
Article in English | MEDLINE | ID: mdl-31871955

ABSTRACT

Fine particulate matter 2.5 (PM2.5) is a harmful air pollutant currently threatening public health. Although many studies have been performed on the general negative effects of PM2.5 in mice and humans, the migration patterns of various immune cells in response to PM2.5 exposure remain unclear. In this study, we aimed to investigate the immune cell migratory response in the lung and the liver of intratracheally PM2.5-inoculated mice. To investigate the migration trajectory of immune cells in the lung and the liver tissues of mice, we employed microscopic tools including two-photon intravital imaging, histological analysis, and transmission electron microscopy. Our data from two-photon intravital imaging showed that there was no significant difference in the number of infiltrated neutrophils in the lung and the liver of PM2.5-treated mice, compared to the nontreated condition. However, from the histological analysis and the transmission electron microscopy after vascular perfusion to remove intravascular leukocytes, we observed that some leukocytes were frequently observed in the lung and the liver of PM2.5-treated mice. Interestingly, quantification of leukocyte population using flow cytometry showed significant increase of neutrophils and macrophages in the lung, but not much in the liver, 24 h post-PM2.5 treatment. These data imply that two-photon intravital imaging of the lung and the liver actually visualized neutrophils, which were adherent to the luminal side of the vasculature. We then conducted mRNA microarray analysis to further observe how PM2.5 affects gene expression patterns in the lung and the liver. PM2.5 treatment changed the mRNA expression associated with the IL-17 signaling pathway in the lung and changed the mRNA expression associated with metabolic pathways in the liver. In summary, these results suggest that the immune response in the lung is distinctly regulated from that in the liver under acute PM2.5-induced inflammation and that these organs consequently are regulated via distinct signaling pathways.


Subject(s)
Disease Susceptibility , Environmental Exposure/adverse effects , Liver/metabolism , Lung/metabolism , Particulate Matter/adverse effects , Respiratory System/metabolism , Signal Transduction/drug effects , Animals , Disease Models, Animal , Inflammation/diagnostic imaging , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Leukocytes/metabolism , Liver/pathology , Lung/pathology , Mice , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/pathology
9.
Immunity ; 51(4): 671-681.e5, 2019 10 15.
Article in English | MEDLINE | ID: mdl-31451397

ABSTRACT

Diet has been suggested to be a potential environmental risk factor for the increasing incidence of autoimmune diseases, yet the underlying mechanisms remain elusive. Here, we show that high glucose intake exacerbated autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE). We elucidated that high amounts of glucose specifically promoted T helper-17 (Th17) cell differentiation by activating transforming growth factor-ß (TGF-ß) from its latent form through upregulation of reactive oxygen species (ROS) in T cells. We further determined that mitochondrial ROS (mtROS) are key for high glucose-induced TGF-ß activation and Th17 cell generation. We have thus revealed a previously unrecognized mechanism underlying the adverse effects of high glucose intake in the pathogenesis of autoimmunity and inflammation.


Subject(s)
Eating/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Glucose/metabolism , Mitochondria/metabolism , Multiple Sclerosis/immunology , Th17 Cells/immunology , Animals , Autoimmunity , Cell Differentiation , Cells, Cultured , Diet , Disease Models, Animal , Humans , Inflammation , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Transgenic , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta/metabolism
10.
Exp Mol Med ; 51(4): 1-13, 2019 04 09.
Article in English | MEDLINE | ID: mdl-30967528

ABSTRACT

Precise spatiotemporal regulation of leukocyte extravasation is key for generating an efficient immune response to injury or infection. The integrins LFA-1(CD11a/CD18) and Mac-1(CD11b/CD18) play overlapping roles in neutrophil migration because they bind the same as well as different ligands in response to extracellular signaling. Using two-photon intravital imaging and transmission electron microscopy, we observed the existence of preferred sites for neutrophil entrance into the endothelial cell monolayer and exit from the basement membrane and pericyte sheath during neutrophil extravasation, namely, hotspots I and II, by elucidating distinctive roles of LFA-1 and Mac-1. To penetrate the vascular endothelium, neutrophils must first penetrate the endothelial cell layer through hotspot I (i.e., the point of entry into the endothelium). Neutrophils frequently remain in the space between the endothelial cell layer and the basement membrane for a prolonged period (>20 min). Subsequently, neutrophils penetrate the basement membrane and pericyte sheath at hotspot II, which is the final stage of exiting the vascular endothelium. To further investigate the roles of LFA-1 and Mac-1, we newly generated LFA-1 FRET (CD11a-YFP/CD18-CFP) mice and Mac-1 FRET (CD11b-YFP/CD18-CFP) mice. Using both FRET mice, we were able to determine that LFA-1 and Mac-1 distinctly regulate the neutrophil extravasation cascade. Our data suggest that the vascular endothelium functions as a double-layered barrier in the steps of neutrophil extravasation. We propose that the harmonized regulation of neutrophil penetration through the endothelium via hotspots I and II may be critical for vascular homeostasis during inflammation.


Subject(s)
CD11b Antigen/metabolism , CD18 Antigens/metabolism , Lymphocyte Function-Associated Antigen-1/metabolism , Neutrophils/metabolism , Animals , Blotting, Western , CD11b Antigen/genetics , CD18 Antigens/genetics , Inflammation/genetics , Inflammation/metabolism , Lymphocyte Function-Associated Antigen-1/genetics , Macrophage-1 Antigen/genetics , Macrophage-1 Antigen/metabolism , Mice , Mice, Inbred C57BL , Microscopy, Electron , Microscopy, Electron, Transmission , Neutrophils/ultrastructure
11.
Front Immunol ; 9: 1681, 2018.
Article in English | MEDLINE | ID: mdl-30116236

ABSTRACT

Disseminated tumor cells in the bone marrow environment are the main cause of systemic metastasis after curative treatment for major solid tumors. However, the detailed biological processes of tumor biology in bone marrow have not been well defined in a real-time manner, because of a lack of a proper in vivo experimental model thereof. In this study, we established intravital imaging models of the bone marrow environment to enable real-time observation of cancer cells in the bone marrow. Using these novel imaging models of intact bone marrow and transplanted bone marrow of mice, respectively, via two-photon microscopy, we could first successfully track and analyze both the distribution and the phenotype of cancer cells in bone marrow of live mouse. Therefore, these novel in vivo imaging models for the bone marrow would provide a valuable tool to identify the biologic processes of cancer cells in a real-time manner in a live animal model.


Subject(s)
Bone Marrow/pathology , Cell Tracking/methods , Neoplasms/pathology , Tumor Microenvironment , Animals , Antimetabolites, Antineoplastic/therapeutic use , Cell Movement/drug effects , Cell Survival/drug effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Flow Cytometry , Humans , Immune Tolerance , Intravital Microscopy , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Mice, Transgenic , Microscopy, Fluorescence, Multiphoton , Models, Animal , Neoplasms/drug therapy , Statistics, Nonparametric , Gemcitabine
12.
Biosci Biotechnol Biochem ; 82(12): 2041-2048, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30130471

ABSTRACT

A new biflavonoid, amentoflavone-7-O-ß-D-glucoside, and thirteen known flavonoids were isolated from the fruits of Juniperus chinensis using a bioactivity-guided method and their tyrosinase inhibitory effects were tested using a mushroom tyrosinase bioassay. Two isolates, hypolaetin-7-O-ß-D-glucoside and quercetin-7-O-α-L-rhamnoside, were found to reduce tyrosinase activity at a concentration of 50 µM. Quercetin-7-O-α-L-rhamnoside attenuated cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells. Molecular docking simulation revealed that quercetin-7-O-α-L-rhamnoside inhibits tyrosinase activity by hydrogen bonding with residues His85, His244, Thr261, and Gly281 of tyrosinase. Abbreviations: EtOH, ethanol; CH2Cl2, dichloromethane; EtOAc, ethylacetate; n-BuOH, n-butanol; MeOH, metanol; CHCl3,chloroform; DMSO, dimethylsulfoxide; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; α-MSH, α-melanocyte stimulating hormone; L-DOPA, L-3, 4-dihydroxyphenylalanine.


Subject(s)
Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Fruit/chemistry , Juniperus/chemistry , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Monophenol Monooxygenase/antagonists & inhibitors , Agaricales/enzymology , Animals , Cell Line, Tumor , Chromatography, High Pressure Liquid , Enzyme Inhibitors/chemistry , Flavonoids/chemistry , Magnetic Resonance Spectroscopy/methods , Mice , Molecular Docking Simulation , Molecular Structure , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet
13.
J Anal Methods Chem ; 2018: 5797152, 2018.
Article in English | MEDLINE | ID: mdl-29862122

ABSTRACT

Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP). Measurement of the concentration of intravenously (i.v.) injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

14.
Cell Adh Migr ; 12(5): 424-431, 2018.
Article in English | MEDLINE | ID: mdl-29733749

ABSTRACT

Neutrophils are highly motile innate immune cells; they actively migrate in response to inflammatory signals. Using two-photon intravital microscopy, we discovered that neutrophils form stable clusters upon phototoxicity at a certain threshold. Without significant damage to the collagen structure of mouse dermis, neutrophils aggregated together with nearby neutrophils. Surprisingly, this in situ neutrophil clustering resulted in rigorous changes of migratory direction. The density of residing neutrophils was also a critical factor affecting clustering. Additionally, we found that the triggering point of neutrophil aggregation was correlated with the structure of the extracellular matrix in the ear dermis, where autofluorescence was strongly observed. This swarming behavior of neutrophils may reflect an unknown communication mechanism of neutrophils during migration under sterile injury.

15.
Immunity ; 48(4): 745-759.e6, 2018 04 17.
Article in English | MEDLINE | ID: mdl-29669252

ABSTRACT

It is unclear how quiescence is enforced in naive T cells, but activation by foreign antigens and self-antigens is allowed, despite the presence of inhibitory signals. We showed that active transforming growth factor ß (TGF-ß) signaling was present in naive T cells, and T cell receptor (TCR) engagement reduced TGF-ß signaling during T cell activation by downregulating TGF-ß type 1 receptor (TßRI) through activation of caspase recruitment domain-containing protein 11 (CARD11) and nuclear factor κB (NF-κB). TGF-ß prevented TCR-mediated TßRI downregulation, but this was abrogated by interleukin-6 (IL-6). Mitigation of TCR-mediated TßRI downregulation through overexpression of TßRI in naive and activated T cells rendered T cells less responsive and suppressed autoimmunity. Naive T cells in autoimmune patients exhibited reduced TßRI expression and increased TCR-driven proliferation compared to healthy subjects. Thus, TCR-mediated regulation of TßRI-TGF-ß signaling acts as a crucial criterion to determine T cell quiescence and activation.


Subject(s)
CARD Signaling Adaptor Proteins/metabolism , CD4-Positive T-Lymphocytes/immunology , Guanylate Cyclase/metabolism , Lymphocyte Activation/immunology , Receptor, Transforming Growth Factor-beta Type I/metabolism , Receptors, Antigen, T-Cell/immunology , Transforming Growth Factor beta1/metabolism , Animals , Autoimmunity/immunology , CARD Signaling Adaptor Proteins/genetics , Cell Line , Cell Proliferation , Colitis/immunology , Colitis/pathology , Disease Models, Animal , Down-Regulation/immunology , Guanylate Cyclase/genetics , HEK293 Cells , Humans , Interleukin-6/immunology , Lupus Erythematosus, Systemic/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/metabolism , Receptor, Transforming Growth Factor-beta Type I/biosynthesis , Signal Transduction/immunology , Transforming Growth Factor beta1/biosynthesis
16.
Biol Pharm Bull ; 41(2): 259-265, 2018.
Article in English | MEDLINE | ID: mdl-29386485

ABSTRACT

Juniperus chinensis, commonly Chinese juniper, has been used for treating inflammatory diseases. This study aimed to investigate anti-atopic dermatitis (AD) effects of standardized J. chinensis fruits extract on murine oxazolone- and 2,4-dinitrochlorobenzene (DNCB)-induced models of AD. Ear swelling, epidermis thickening, and eosinophils infiltration in the oxazolone-mediated dermatitis of BALB/c mice were significantly reduced upon topical application of J. chinensis fruits 95% EtOH extract (JCE). Besides, transdermal administration of JCE to SKH-1 hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing transepidermal water loss and improving skin hydration. Decreased total serum immunoglobulin E (IgE) and interleukin (IL)-4 levels could be observed in atopic dorsal skin samples of JCE-treated group. According to the phytochemical analysis, JCE was found to contain isoscutellarein-7-O-ß-D-xyloside, cupressuflavone, and amentoflavone as main compounds. Therapeutic attempts with the J. chinensis fruits might be useful in the treatment of AD and related skin inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dermatitis, Atopic/prevention & control , Fruit/chemistry , Juniperus/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Skin/drug effects , Adjuvants, Immunologic/toxicity , Administration, Cutaneous , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/analysis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Biflavonoids/administration & dosage , Biflavonoids/analysis , Biflavonoids/chemistry , Biflavonoids/therapeutic use , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Dinitrochlorobenzene/toxicity , Female , Flavonoids/administration & dosage , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/therapeutic use , Fruit/growth & development , Glycosides/administration & dosage , Glycosides/analysis , Glycosides/chemistry , Glycosides/therapeutic use , Immunoglobulin E/analysis , Interleukin-4/blood , Irritants/toxicity , Juniperus/growth & development , Mice, Hairless , Mice, Inbred BALB C , Molecular Structure , Oxazolone/toxicity , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Republic of Korea , Skin/immunology , Skin/metabolism , Skin/pathology
17.
J Vis Exp ; (132)2018 02 06.
Article in English | MEDLINE | ID: mdl-29443058

ABSTRACT

Sepsis is a type of severe infection that can cause organ failure and tissue damage. Although the mortality and morbidity rates associated with sepsis are extremely high, no direct treatment or organ-related mechanism has been examined in detail in real time. The liver is the key organ that manages toxins and infections in the human body. Herein, we aimed to perform intravital imaging of mouse liver after induction of endotoxemia in order to track the motility of immune cells, such as neutrophils and liver capsular macrophages (LCMs). Accordingly, we designed a novel surgical method for exposure of the liver with minimally invasive surgery. Mice were intraperitoneally injected with lipopolysaccharide (LPS), a common endotoxin. Using our novel surgical approach for exposure and intravital imaging of the mouse liver, we found that neutrophil recruitment in LPS-treated LysM-green fluorescent protein (GFP) mouse liver was increased compared with that in phosphate-buffered saline-treated liver. After LPS treatment, the number of neutrophils increased significantly with time. Additionally, using CX3Cr1-GFP mice, we successfully visualized liver resident macrophages called LCMs. Therefore, to investigate the efficacy of new reagents to control immune mobility in vivo, determining the motility and morphology of neutrophils and LCMs in the liver may allow us to identify therapeutic effect in organ failure and tissue damage caused by leukocytes activation in sepsis.


Subject(s)
Intravital Microscopy/methods , Leukocytes/drug effects , Lipopolysaccharides/therapeutic use , Liver/physiopathology , Animals , Humans , Lipopolysaccharides/pharmacology , Mice
18.
J Ethnopharmacol ; 214: 160-167, 2018 Mar 25.
Article in English | MEDLINE | ID: mdl-29258854

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Juniperus rigida have been used in Korean traditional medicine for the treatment of inflammatory diseases in humans such as rheumatoid arthritis. AIM OF THE STUDY: This study aimed to investigate the anti-atopic properties of J. rigida fruit in in vivo murine atopic dermatitis (AD) models. METHODS AND RESULTS: BALB/c mouse ears ad SKH-1 hairless mice stimulated with oxazolone (4 weeks) and DNCB (3 weeks), respectively, were treated with the 1% Juniperus rigida fruit EtOH extract (JFE). The JFE improved AD symptoms in both oxazolone- and DNCB-induced AD mice by accelerating skin barrier recovery function and suppressing the overproduction of serum immunoglobulin E (IgE) and interleukin 4 (IL-4). The JFE was found to contain isoscutellarein-7-O-ß-xylopyranoside, cupressuflavone, podocarpusflavone A, and hinokiflavone as major components based on phytochemical analysis. Eight flavonoids were isolated from JFE, and of those, cupressuflavone and isoscutellarein-7-O-ß-xylopyranoside strongly down-regulated IL-4 expression and ß-hexosaminidase release in RBL-2H3 cells. CONCLUSION: Therapeutic attempts with J. rigida fruit and its active components might be useful in treating AD and related skin inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dermatitis, Atopic/prevention & control , Dinitrochlorobenzene , Juniperus , Oxazolone , Plant Extracts/pharmacology , Skin/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cell Line, Tumor , Dermatitis, Atopic/blood , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/immunology , Disease Models, Animal , Female , Fruit/chemistry , Immunoglobulin E/blood , Interleukin-4/blood , Juniperus/chemistry , Mice, Hairless , Mice, Inbred BALB C , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal , Rats , Skin/immunology , Skin/metabolism , beta-N-Acetylhexosaminidases/metabolism
19.
Immune Netw ; 16(6): 317-321, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28035206

ABSTRACT

Immune cells (leukocytes or white blood cells) move actively and sensitively based on body conditions. Despite their important role as protectors inside the body, it is difficult to directly observe the spatiotemporal momentum of leukocytes. With advances in imaging technology, the introduction of two-photon microscopy has enabled researchers to look deeper inside tissues in a three-dimensional manner. In observations of immune cell movement along the blood vessel, vascular permeability and innate immune cell movements remain unclear. Here, we describe the neutrophil extravasation cascade, which were observed using a two-photon intravital imaging technique. We also provide evidence for novel mechanisms such as neutrophil body extension and microparticle formation as well as their biological roles during migration.

20.
Biosci Biotechnol Biochem ; 80(12): 2311-2317, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27492585

ABSTRACT

The fruits of Juniperus communis have been traditionally used in the treatment of skin diseases. In our preliminary experiment, the MeOH extract of J. communis effectively suppressed mushroom tyrosinase activity. Three monoflavonoids and five biflavonoids were isolated from J. communis by bioassay-guided isolation and their inhibitory effect against tyrosinase was evaluated. According to the results of all isolates, hypolaetin 7-O-ß-xylopyranoside isolated from J. communis exhibited most potent effect of decreasing mushroom tyrosinase activity with an IC50 value of 45.15 µM. Further study provided direct experimental evidence for hypolaetin 7-O-ß-D-xylopyranoside-attenuated tyrosinase activity in α-MSH-stimulated B16F10 murine melanoma cell. Hypolaetin 7-O-ß-D-xylopyranoside from the EtOAc fraction of J. communis was also effective at suppressing α-MSH-induced melanin synthesis. This is the first report of the enzyme tyrosinase inhibition by J. communis and its constituent. Therapeutic attempts with J. communis and its active component, hypolaetin 7-O-ß-D-xylopyranoside, might be useful in treating melanin pigmentary disorders.


Subject(s)
Flavonoids/pharmacology , Fruit/chemistry , Juniperus/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Animals , Cell Line, Tumor , Flavonoids/chemistry , Flavonoids/isolation & purification , Melanins/metabolism , Mice , alpha-MSH/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL