ABSTRACT
Due to insufficient amount of soluble phosphate and poor persistence of traditional chemical phosphate fertilizers in agricultural soils, the eco-friendly and sustainable phosphorus sources for crops are urgently required. The efficient phosphate-releasing fungal strain designated y2 was isolated and identified by the internal transcribed spacer of rDNA as Penicillium oxalicum y2. When lecithin, Ca3(PO4)2, or ground phosphate rock were separately used as sole phosphorus source, different phosphate-releasing modes were observed. The strain y2 was able to release as high as 2090 mg/L soluble phosphate within 12 days of incubation with Ca3(PO4)2 as sole phosphorus source. In the culture solution, high concentration of oxalic, citric, and malic acids and high phosphatase activity were detected. The organic acids contributed to solubilizing inorganic phosphate sources, while phosphatase was in charge of the mineralization of organic phosphorus lecithin. Afterwards, the fungus culture was applied to the soil with rape growing. During 50 days of incubation, the soil's available phosphate concentration increased by three times compared with the control, the dry weight of rape increased by 78.73%, and the root length increased by 38.79%. The results illustrated that P. oxalicum y2 possessed both abilities of solubilizing inorganic phosphorus and mineralizing organic phosphorus, which have great potential application in providing biofertilizer for modern agriculture.
Subject(s)
Penicillium/metabolism , Phosphates/metabolism , Phosphorus/metabolism , Soil Microbiology , Biological Availability , Brassica napus/growth & development , Carbon/metabolism , Carboxylic Acids/metabolism , DNA, Ribosomal Spacer/genetics , Nitrogen/metabolism , Penicillium/classification , Penicillium/genetics , Penicillium/isolation & purification , Phosphates/pharmacokinetics , Phosphoric Monoester Hydrolases/metabolism , Phylogeny , Soil/chemistryABSTRACT
Mushroom Inonotus sanghuang has been characterized as a traditional medicine in China and has pharmacological activities to treat inflammation, gastroenteric dysfunction, and cancer. Recently, we reported the impact of Inonotus sanghuang extract (ISE) from ethyl acetate fraction on bleomycin (BLM)-induced acute lung injury in mice. Here, we aimed to investigate ISE's impact on pulmonary fibrosis using in vivo and in vitro models and the underlying mechanisms. To evaluate pulmonary fibrosis, female C57BL/6 mice fed ISE (0% or 0.6% in diet) for 4 weeks were instilled intratracheally with BLM and then continued the same diet before the end of the experiment. A549 cells were used to evaluate the epithelial-mesenchymal transition (EMT). Feeding ISE improved BLM-treated mice's survival via decreasing lung infiltrating cells and fibrosis, followed by reducing hydroxyproline content, collagen deposition, and mesenchymal markers (α-SMA and vimentin) while increasing epithelial marker E-cadherin. ISE also suppressed the TGF-ß expression, Smad2/3 phosphorylation, and EMT-related transcription factor Snail upon BLM instillation. Iin vitro study demonstrated that ISE inhibited TGF-ß-induced EMT-like phenotype and cell behaviors, the expression of α-SMA and vimentin, and prevented E-cadherin reduction of A549 cells. Consistent with in vivo study, ISE abrogated p-Smad2/3, and Snail expression. Finally, the influence of ISE on EMT was not due to ISE toxicity. Our findings indicated that ISE effectively attenuated BLM-induced lung fibrosis. These ISE properties were thought to be involved in interfering TGF-ß, Smad2/3 phosphorylation, and EMT process, suggesting that the material has the potential health benefits to improve lung fibrosis.
Subject(s)
Basidiomycota , Epithelial-Mesenchymal Transition/drug effects , Lung/drug effects , Pulmonary Fibrosis/prevention & control , Respiratory System Agents/pharmacology , Transforming Growth Factor beta/metabolism , A549 Cells , Animals , Basidiomycota/chemistry , Bleomycin , Bronchoalveolar Lavage Fluid/chemistry , Cell Movement/drug effects , Collagen Type I/metabolism , Disease Models, Animal , Female , Humans , Lung/metabolism , Lung/pathology , Mice, Inbred C57BL , Phosphorylation , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Respiratory System Agents/isolation & purification , Signal Transduction , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Snail Family Transcription Factors/metabolismABSTRACT
Mushroom Phellinus linteus ("Sanghuang" in Chinese) is a popular medicinal polypore used to treat several disorders through its various biological functions. Inonotus sanghuang is claimed to produce general immune-potentiating and strengthening, anti-inflammatory, anti-tumor and anti-microbial properties, but its effect on acute lung inflammation and oxidative stress are not clearly understood. To determine the effect and mechanism of the polyphenols-rich ethyl acetate fraction from wild I. sanghuang extract (ISE) on acute lung injury (ALI) induced by bleomycin (BLM), female C57BL/6 mice were fed ISE (0%, 0.15% or 0.6% in diet) for 4â¯weeks prior to challenge with BLM. Bronchoalveolar lavage fluid (BALF) from lung, spleen and lung tissues were collected on day 3 after BLM challenge for histological, oxidative stress, molecular and biochemical analysis. ISE supplementation improved pathological features in lung injury scores and reduced lung wet-to-dry ratios. Moreover, ISE reduced inflammatory cell infiltration and the pro-inflammatory cytokines including IL-1ß, IL-6 and TNF-α in BALF, decreased the MPO activity and the MDA level and increased the SOD, CAT and GSH-Px activities in lung tissue homogenates. Further mechanism analysis demonstrated that dietary ISE inhibited NF-κB signal. Finally, peripheral immune function analysis showed that ISE had less effect on immune response including splenocyte producing inflammatory cytokines and T cell proliferation except for IL-1ß and IL-2. Our findings indicate the possibility that dietary ISE attenuates ALI induced by BLM through correcting the inflammation and oxidation balance at least in part via inhibiting NF-κB signal in vivo, suggesting that ISE might be a valuable medicinal food effective in improving lung injury.
Subject(s)
Acute Lung Injury/drug therapy , Plant Extracts/pharmacology , Acute Lung Injury/chemically induced , Agaricales/isolation & purification , Agaricales/metabolism , Animals , Antioxidants/pharmacology , Bleomycin/pharmacology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/metabolism , Female , Inflammation/pathology , Interleukin-1beta/pharmacology , Lung/pathology , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Phellinus , Polyphenols/isolation & purification , Polyphenols/pharmacology , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Over the last decade, ensemble visualization has witnessed a significant development due to the wide availability of ensemble data, and the increasing visualization needs from a variety of disciplines. From the data analysis point of view, it can be observed that many ensemble visualization works focus on the same facet of ensemble data, use similar data aggregation or uncertainty modeling methods. However, the lack of reflections on those essential commonalities and a systematic overview of those works prevents visualization researchers from effectively identifying new or unsolved problems and planning for further developments. In this paper, we take a holistic perspective and provide a survey of ensemble visualization. Specifically, we study ensemble visualization works in the recent decade, and categorize them from two perspectives: (1) their proposed visualization techniques; and (2) their involved analytic tasks. For the first perspective, we focus on elaborating how conventional visualization techniques (e.g., surface, volume visualization techniques) have been adapted to ensemble data; for the second perspective, we emphasize how analytic tasks (e.g., comparison, clustering) have been performed differently for ensemble data. From the study of ensemble visualization literature, we have also identified several research trends, as well as some future research opportunities.
ABSTRACT
Autoimmune disease is highly prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have anti-inflammatory and antioxidant properties. Using the experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we determined the effect of dietary naringenin (0.5%) on autoimmune disease. We found that naringenin reduced the incidence, delayed the onset, and attenuated the symptoms of EAE, which were accompanied by reduced immune cell infiltration and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4+ T cell subsets Th1, Th9, and Th17 cells together with their respective transcription factors T-bet, PU.1, and RORγt were reduced in both the central nervous system (CNS) and lymph nodes of EAE mice fed naringenin while no difference was found in Th2 and regulatory T cell (Treg) populations in either CNS or lymph nodes between the two groups. We further showed that pathologic T cell proliferation induced by ex vivo re-stimulation with MOG35-55 and proinflammatory cytokines IL-6 and TNF-α were lower in naringenin-fed mice than in the control mice. Additionally, we found that naringenin treatment inhibited mRNA expression of CXCL10 (Th1 recruiting chemokine), vascular cell adhesion molecule-1 (VCAM-1), and VLA-4 (VCAM-1 ligand) in the CNS of EAE mice. Altogether, these results indicate that naringenin may have a potential to ameliorate autoimmune disease by favorably modulating autoimmune response.
Subject(s)
Autoimmunity/drug effects , Encephalomyelitis, Autoimmune, Experimental/diet therapy , Flavanones/pharmacology , Animals , Central Nervous System/drug effects , Central Nervous System/metabolism , Central Nervous System/pathology , Chemokines/metabolism , Dietary Supplements , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Mice, Inbred C57BL , Myelin Sheath/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/immunology , Transcription Factors/metabolismABSTRACT
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common debilitating disease and there has not been consistently effective treatment. We aimed to evaluate all available literature regarding the efficacy and safety of sacral neuromodulation (SNM) for refractory BPS/IC. A comprehensive search of Pubmed, Web of Science and Cochrane Library through May 2016 was conducted. A total of 17 studies enrolling 583 patients were identified. Pooled analyses demonstrated that SNM was associated with great reduction in pelvic pain (weighted mean difference [WMD] -3.99; 95% confidence interval [CI] -5.22 to -2.76; p < 0.00001), Interstitial Cystitis Problem and Symptom Index scores (WMD -6.34; 95% CI -9.57 to -3.10; p = 0.0001; and WMD -7.17; 95% CI -9.90 to -4.45; p < 0.00001, respectively), daytime frequency (WMD -7.45; 95% CI -9.68 to -5.22; p < 0.00001), nocturia (WMD -3.01; 95% CI -3.56 to -2.45; p < 0.00001), voids per 24 hours (WMD -9.32; 95% CI -10.90 to -7.74; p < 0.00001) and urgency (WMD -1.08; 95% CI -1.79 to -0.37; p = 0.003) as well as significant improvement in average voided volume (WMD 95.16 ml; 95% CI 63.64 to 126.69; p < 0.0001). The pooled treatment success rate was 84% (95% CI 76% to 91%). SNM-related adverse events were minimal. Current evidence indicates that SNM might be effective and safe for treating refractory BPS/IC.
Subject(s)
Cystitis, Interstitial/therapy , Transcutaneous Electric Nerve Stimulation/methods , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Humans , Spinal Cord/physiology , Treatment OutcomeABSTRACT
Presence of unmetabolized folic acid in plasma, which is indicative of folic acid intake beyond the metabolic capacity of the body, is associated with reduced natural killer (NK) cell cytotoxicity in postmenopausal women ≥50years. NK cells are cytotoxic lymphocytes that are part of the innate immune system critical for surveillance and defense against virus-infected and cancer cells. We determined if a high folic acid diet can result in reduced NK cell cytotoxicity in an aged mouse model. Female C57BL/6 mice (16-month-old) were fed an AIN-93M diet with the recommended daily allowance (1× RDA, control) or 20× RDA (high) folic acid for 3months. NK cytotoxicity was lower in splenocytes from mice fed a high folic acid diet when compared to mice on control diet (P<.04). The lower NK cell cytotoxicity in high folic acid fed mice could be due to their lower mature cytotoxic/naïve NK cell ratio (P=.03) when compared to the control mice. Splenocytes from mice on high folic acid diet produced less interleukin (IL)-10 when stimulated with lipopolysaccharide (P<.05). The difference in NK cell cytotoxicity between dietary groups was abolished when the splenocytes were supplemented with exogenous IL-10 prior to assessment of the NK cytotoxicity, suggesting that the reduced NK cell cytotoxicity of the high folic acid group was at least partially due to reduced IL-10 production. This study demonstrates a causal relationship between high folic acid intake and reduced NK cell cytotoxicity and provides some insights into the potential mechanisms behind this relationship.
Subject(s)
Aging/immunology , Cytotoxicity, Immunologic , Folic Acid/administration & dosage , Killer Cells, Natural/immunology , Animals , Female , Mice , Mice, Inbred C57BLABSTRACT
A series of red to near-infrared (NIR) emitting quantum dots (QDs) with spherical morphologies and tunable photoluminescence (PL) properties have been synthesized by a facile organic route using octadecene (ODE) as solvent and oleic acid (OA) as single capping agent. CdSe cores with the average size of 4.5 nm display the typical optical behaviors with the PL emission peak around 610 nm. The coating CdZnS shells are introduced on the surface of CdSe cores for improving the photostability and PL efficiency of the initial QDs. As the thickness of CdZnS shells increasing, the gradual red-shift of emission wavelength varying from 617 to 634 nm of the resulting QDs can be observed, along with the remarkable increase of PL quantum yield (QY). The composition-dependent CdTe(x)Se(1-x) (CdTeSe) cores with the emission in NIR region are easily carried out by adjusting the molar ratio of Se/Te. The abnormal variation of optical bowling effect is mainly ascribed to the composition effect of alloyed QDs. Compared with CdTe0.1Se0.9/CdZnS core/shell QDs, the introducing of CdZnS shells on CdTe0.05Se0.95 cores can exhibit better passivation effect on surface status, consequently leading to the red-shifted emission peaks in the range of 739-752 nm with the maximum PL QY reaching up to 45.09%. The unique PL properties of CdTeSe-based QDs in the red to NIR range make these core/shell QDs attractive for future biological sensing and labeling applications.
Subject(s)
Cadmium Compounds/chemistry , Luminescent Agents/chemistry , Quantum Dots , Selenium/chemistry , Spectroscopy, Near-Infrared/methods , Tellurium/chemistry , Zinc/chemistryABSTRACT
We previously showed that dietary white button mushrooms (WBMs) enhanced natural killer cell activity and that in vitro WBM supplementation promotes maturation and function of dendritic cells (DCs). The current study investigated whether WBM consumption would enhance pathogen-specific immune response using a Salmonella vaccination and infection animal model. C57BL/6 mice were fed diets containing 0%, 2%, or 5% WBM for 4 wk before oral vaccination with live attenuated Salmonella typhimurium SL1479. Four weeks after immunization, mice were orally infected with virulent Salmonella typhimurium SL1344. Immunization increased animal survival and, among immunized mice, the 2% WBM group had a higher survival rate than the other groups. Next, we fed mice 2% WBMs to determine the immunological mechanism underlying the WBM-potentiated protective effect. We found that WBM supplementation increased Salmonella-specific blood immunoglobulin (Ig) G and fecal IgA concentrations. WBM-fed mice also had a higher IgG2a and unchanged IgG1 production, leading to an elevated IgG2a:IgG1 ratio and indicating an enhanced T helper 1 response. Consistent with these results, WBM-fed mice had higher interferon-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17A production and unchanged IL-4 production in their splenocytes after polyclonal (anti-CD3/CD28) or antigen-specific stimulation. Furthermore, WBM-fed mice had more DCs in the spleen, and these DCs expressed higher levels of activation markers CD40 and major histocompatibility complex-II. These mice also produced more IL-12 and TNF-α postimmunization. Together, these results suggest that WBMs may improve Salmonella vaccine efficacy through an enhanced adaptive immune response.
Subject(s)
Agaricales/chemistry , Dietary Supplements , Foodborne Diseases/prevention & control , Salmonella Vaccines/immunology , Adaptive Immunity , Animals , Dendritic Cells/immunology , Disease Models, Animal , Female , Foodborne Diseases/immunology , Immunoglobulin A/immunology , Immunoglobulin A/metabolism , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/metabolism , Interleukin-17/metabolism , Mice , Mice, Inbred C57BL , Salmonella Vaccines/chemistry , Salmonella typhimurium , Spleen/cytology , Spleen/immunology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Current vaccines for influenza do not fully protect the aged against influenza infection. Although wolfberry (goji berry) has been shown to improve immune response, including enhanced antibody production, after vaccination in the aged, it is not known if this effect would translate to better protection after influenza infection, nor is its underlying mechanism well understood. To address these issues, we conducted a study using a 2 × 2 design in which aged male mice (20-22 mo) were fed a control or a 5% wolfberry diet for 30 d, then immunized with an influenza vaccine or saline (control) on days 31 and 52 of the dietary intervention, and finally challenged with influenza A/Puerto Rico/8/34 virus. Mice fed wolfberry had higher influenza antibody titers and improved symptoms (less postinfection weight loss) compared with the mice treated by vaccine alone. Furthermore, an in vitro mechanistic study showed that wolfberry supplementation enhanced maturation and activity of antigen-presenting dendritic cells (DCs) in aged mice, as indicated by phenotypic change in expression of DC activation markers major histocompatibility complex class II, cluster of differentiation (CD) 40, CD80, and CD86, and functional change in DC production of cytokines interleukin-12 and tumor necrosis factor-α as well as DC endocytosis. Also, adoptive transfer of wolfberry-treated bone marrow DCs (loaded with ovalbumin(323-339)-peptide) promoted antigen-specific T cell proliferation as well as interleukin-4 and interferon-γ production in CD4(+) T cells. In summary, our data indicate that dietary wolfberry enhances the efficacy of influenza vaccination, resulting in better host protection to prevent subsequent influenza infection; this effect may be partly attributed to improved DC function.
Subject(s)
Dietary Supplements , Influenza A virus/immunology , Influenza Vaccines/immunology , Lycium , Orthomyxoviridae Infections/diet therapy , Phytotherapy , Plant Preparations/therapeutic use , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Animals , Antibodies/blood , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Bone Marrow/drug effects , Bone Marrow/immunology , CD4-Positive T-Lymphocytes/metabolism , CD40 Antigens/metabolism , Cytokines/biosynthesis , Dendritic Cells/drug effects , Endocytosis/drug effects , Fruit , Genes, MHC Class II , Immunization , Male , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Ovalbumin , Peptide Fragments , Plant Preparations/pharmacology , Weight Loss/drug effectsABSTRACT
BACKGROUND: Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-inflammation properties while piperine, another bioactive phenolic compound present in pepper spice, can enhance the bioavailability and efficacy of curcumin. This study sought to determine if curcumin could potentiate CR's beneficial effect on immune and inflammatory responses in obesity developed in mice by feeding high-fat diet (HFD). METHODS: Mice were fed a HFD for 22 wk and then randomized into 5 groups: one group remained on HFD ad libitum and the remaining 4 groups were fed a 10% CR (reduced intake of HFD by 10% but maintaining the same levels of micronutrients) in the presence or absence of curcumin and/or piperine for 5 wk, after which CR was increased to 20% for an additional 33 wk. At the end of the study, mice were sacrificed, and spleen cells were isolated. Cells were stimulated with T cell mitogens, anti-CD3/CD28 antibodies, or lipopolysaccharide to determine T cell proliferation, cytokine production, and CD4+ T cell subpopulations. RESULTS: Compared to HFD control group, all CR mice, regardless of the presence of curcumin and/or piperine, had lower body weight and fat mass, lower levels of blood glucose and insulin, and fewer total spleen cells but a higher percentage of CD4+ T cells. Additionally, they demonstrated lower production of pro-inflammatory cytokines IL-1ß and TNF-α, a trend toward lower IL-6, and lower production of PGE2, a lipid molecule with pro-inflammatory and T cell-suppressive properties. Mice with CR alone had higher splenocyte proliferation and IL-2 production, but this effect of CR was diminished by spice supplementation. CR alone or in combination with spice supplementation had no effect on production of cytokines IL-4, IL-10, IFN-γ, and IL-17, or the proportion of different CD4+ T cell subsets. CONCLUSION: CR on an HFD favorably impacts both metabolic and immune/inflammatory profiles; however, the presence of curcumin and/or piperine does not amplify CR's beneficial effects.
ABSTRACT
CD4(+) T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We and others have previously shown that epigallocatechin-3-gallate (EGCG) attenuates experimental autoimmune encephalomyelitis (EAE) and alters CD4(+) T cell subpopulations. In this study, we investigated how EGCG impacts differentiation of naïve CD4(+) T cells into different effector lineages and report that EGCG impeded Th1, Th9, and Th17 differentiation and prevented IL-6-induced suppression of Treg development. We further showed that EGCG inhibited T-bet, PU.1, and RORγt, the specific transcription factors for Th1, Th9, and Th17 differentiation, respectively. These effects, in turn, may be mediated by EGCG-induced downregulation of transducers p-STAT1 and p-STAT4 for Th1, and p-STAT3 for Th17. EGCG-induced change in Th17/Treg balance may be mediated by its inhibition of IL-6 signaling because EGCG inhibited soluble IL-6R, membrane gp130, and IL-6-induced phosphorylation of STAT3. This notion was further supported by the in vivo results showing inhibited IL-6 and soluble IL-6R but increased soluble gp130 levels in plasma from EAE mice fed EGCG. Together, our results suggest that EGCG modulates development of CD4(+) T cell lineages through impacting their respective and interactive regulatory networks ultimately leading to an attenuated autoimmune response.
Subject(s)
CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , Catechin/analogs & derivatives , Cell Differentiation/drug effects , Tea/chemistry , Animals , CD4-Positive T-Lymphocytes/immunology , Catechin/pharmacology , Cell Differentiation/immunology , Female , Interleukin-6/pharmacology , Mice , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Receptors, Interleukin/metabolism , Receptors, Interleukin-6/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Th1 Cells/cytology , Th1 Cells/drug effects , Th17 Cells/cytology , Th17 Cells/drug effects , Th17 Cells/metabolism , Th2 Cells/cytology , Th2 Cells/drug effectsABSTRACT
Despite the availability of vaccines, influenza is a considerable public health problem, which emphasizes the need for development of additional strategies to enhance host defense against influenza. Wolfberry, or goji berry, long used as a medicinal food in China, has recently been shown to improve immune response in mice. Because immune response plays a key role in the body's defense against pathogens, we hypothesized that wolfberry may increase host resistance to influenza infection by enhancing immune response. To test this hypothesis, we fed adult mice (4 mo old) a milk-based preparation of wolfberry called Lacto-Wolfberry (LWB) for 4 wk and then infected them with influenza A/Puerto Rico/8/34 (H1N1) while continuing the same experimental diets. Viral titer, lung pathology, and immune response were determined at different time points postinfection. LWB supplementation prevented infection-induced weight loss and reduced lung pathology on days 6 and 9 postinfection (P < 0.05). LWB-fed mice showed overall, significantly higher concanavalin A-induced IL-2 production (P < 0.05). Furthermore, we found positive correlations between weight loss and lung viral titer, pathology score, TNFα, and IL-6 production as well as negative correlations with T cell proliferation and IL-2 production (all P ≤ 0.05). These results indicate that LWB supplementation can attenuate symptoms and pathology of influenza infection by decreasing inflammatory cytokines in lungs while enhancing systemic T cell-mediated function as measured by their ability to produce IL-2.
Subject(s)
Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Lycium , Orthomyxoviridae Infections/prevention & control , Animal Feed/analysis , Animals , Diet , Dietary Supplements , Glutathione/metabolism , Glutathione Disulfide/metabolism , Killer Cells, Natural/physiology , Lung/metabolism , Lymphocytes/physiology , Male , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Random Allocation , Spleen/cytology , Spleen/metabolismABSTRACT
One of the proposed health benefits of consuming green tea is its protective effect on autoimmune diseases. Research on the immunopathogenesis of autoimmune diseases has made significant progression in the past few years and several key concepts have been revised. T cells, particularly CD4(+) T helper (Th) cells, play a key role in mediating many aspects of autoimmune diseases. Upon antigenic stimulation, naïve CD4(+) T cells proliferate and differentiate into different effector subsets. Th1 and Th17 cells are the pro-inflammatory subsets of Th cells responsible for inducing autoimmunity whereas regulatory T cells (Treg) have an antagonistic effect. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to improve symptoms and reduce the pathology in some animal models of autoimmune diseases. Whether or not EGCG's effect is mediated through its impact on Th17 and Treg development has not been studied. We conducted a series of studies to investigate EGCG's effect on CD4(+) T cell proliferation and differentiation as well as its impact on the development of autoimmune disease. We first observed that EGCG inhibited CD4(+) T cell expansion in response to either polyclonal or antigen specific stimulation. We then determined how EGCG affects naïve CD4(+) T cell differentiation and found that it impeded Th1 and Th17 differentiation and prevented IL-6-induced inhibition on Treg development. We further demonstrated that EGCG inhibited Th1 and Th17 differentiation by downregulating their corresponding transcription factors (STAT1 and T-bet for Th1, and STAT3 and RORγt for Th17). These effects provide further explanation for previous findings that administration of EGCG by gavage to experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis (MS), reduced the clinical symptoms, brain pathology, and proliferation and TNF-α production of encephalitogenic T cells. Upon further investigating the working mechanisms for EGCG's protective effect in the EAE model, we showed that dietary EGCG dose-dependently attenuated the disease's severity. This protective effect of EGCG is associated with the suppressed proliferation of autoreactive T cells, reduced production of pro-inflammatory cytokines, decreased Th1 and Th17, and increased Treg populations in lymphoid tissues and central nervous system. EGCG-induced shifts in CD4(+) T cell subsets in EAE mice are accompanied by the corresponding changes in their regulator molecules. Recent studies have also highlighted the critical role of Th17/Treg balance in the pathogenesis of rheumatoid arthritis (RA). EGCG has been shown to be anti-inflammatory and protective in several studies using animal models of inflammatory arthritis, but research, at the best, only to start looking into the mechanisms with a focus on T cells. Overall, future research should fully incorporate the current progress in autoimmunity into the study design to expand the power of evaluating EGCG's efficacy in treating autoimmune diseases. Data from human studies are essentially absent and thus are urgently needed.
Subject(s)
Autoimmune Diseases/immunology , Catechin/analogs & derivatives , Immunologic Factors/pharmacology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tea/chemistry , Animals , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Catechin/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/immunology , Humans , Immunity, Cellular/drug effectsABSTRACT
The green tea component epigallocatechin-3-gallate (EGCG) may be beneficial in autoimmune diseases; however, the underlying mechanisms are not well understood. In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis, an animal model for human multiple sclerosis, and the underlying mechanisms. Female C57BL/6 mice were fed EGCG (0%, 0.15%, 0.3%, and 0.6% in diet) for 30 days and then immunized with specific antigen myelin oligodendrocyte glycoprotein 35-55. EGCG dose dependently attenuated clinical symptoms and pathological features (leukocyte infiltration and demyelination) in the central nervous system and inhibited antigen-specific T-cell proliferation and delayed-type hypersensitivity skin response. We further showed that EGCG reduced production of interferon-γ, IL-17, IL-6, IL-1ß, and tumor necrosis factor-α; decreased types 1 and 17 helper T cells (Th1 and Th17, respectively); and increased regulatory T-cell populations in lymph nodes, the spleen, and the central nervous system. Moreover, EGCG inhibited expression of transcription factors T-box expressed in T cells and retinoid-related orphan receptor-γt, the specific transcription factor for Th1 and Th17 differentiation, respectively; the plasma levels of intercellular adhesion molecule 1; and CCR6 expression in CD4(+) T cells. These results indicate that EGCG may attenuate experimental autoimmune encephalomyelitis autoimmune response by inhibiting immune cell infiltration and modulating the balance among pro- and anti-autoimmune CD4(+) T-cell subsets. Thus, we identified a novel mechanism that underlies EGCG's beneficial effect in autoimmune disease.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Catechin/analogs & derivatives , Encephalomyelitis, Autoimmune, Experimental/prevention & control , Neuroprotective Agents/pharmacology , T-Lymphocyte Subsets/drug effects , Animals , CD4-Positive T-Lymphocytes/immunology , Catechin/pharmacology , Cell Proliferation , Cytokines/metabolism , Demyelinating Diseases/prevention & control , Dietary Supplements , Down-Regulation , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Mice , Mice, Inbred C57BL , Monocytes/metabolism , Multiple Sclerosis/immunology , Multiple Sclerosis/prevention & control , Myelin Proteins/antagonists & inhibitors , Myelin-Oligodendrocyte Glycoprotein , Neuritis/prevention & control , Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors , Random Allocation , T-Box Domain Proteins/antagonists & inhibitors , T-Lymphocyte Subsets/immunologyABSTRACT
OBJECTIVE: To evaluate the efficacy and adverse reaction of total glucosides of paeony (TGP) combined with sulfasalazine (SSZ) in the treatment of ankylosing spondylitis (AS). METHODS: Sixty-seven AS patients were randomly assigned to 2 groups: the treatment group (34 cases) treated with TGP and SSZ, the control group (33 cases) with methotrexate (MTX) and SSZ. Changes of clinical efficacy related indexes including lumber pain index, morning stiffness time, peripheral joint pain index, thoracic expansion, Schober test, Bath AS disease active index (BASDAI), Bath AS functional index (BASFI), the levels of erythrocyte sedimentation (ESR) and C-reactive protein (CRP), and X-ray of sacroiliac joint were observed. RESULTS: The clinical efficacy indexes were significantly improved after treatment in the two groups (P < 0.05). Except that the improvement of lumber pain index and peripheral joint pain index was better in the treatment group than that in the control group (P < 0.05), no significant difference was found in the other indexes between the two groups. The occurrence of adverse reation was less in the treatment group than in the control group (P < 0.05). CONCLUSION: TGP treatment combined with SSZ shows favorable effect on AS with less and milder adverse reaction.