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1.
Toxicol Mech Methods ; : 1-16, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33467949

RESUMO

Smokeless tobacco products provide an alternative to cigarettes; however, smokeless tobacco is carcinogenic and harmful to human health. This study evaluated the toxicological effects of snus extracts and cigarette smoke total particulate matter (TPM) on human umbilical vein endothelial cells (HUVECs). Treated cells were examined for cell viability, reactive oxygen species (ROS), apoptosis, and inflammatory cytokines. Moreover, we explored the mechanism of programmed cell death induced by snus. The results showed that snus extracts significantly inhibited cell viability in a dose-dependent manner. ROS was significantly increased in treatment groups, and anti-oxidant treatment could not prevent snus extract-induced cell death. Snus extracts induced apoptosis, DNA damage, activation and cleavage of caspase-3 and caspase-8, pathway-related gene change, and interleukin (IL)-6 and IL-8 release in HUVECs. Snus extracts exposure may induce cytotoxicity, ROS generation, inflammatory cytokines release, and apoptosis or DNA damage through intrinsic and extrinsic pathways in HUVECs.

2.
Aging Clin Exp Res ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767273

RESUMO

BACKGROUND: Major depressive disorder is a global public health problem among older adults. Many studies show that problem-solving therapy (PST) is a cognitive behavioral approach that can effectively treat late-life depression. AIM: To summarize and assess the effects of PST on major depressive disorders in older adults. METHODS: We searched the PubMed, Web of Science, Cochrane Library, EMBASE, MEDLINE, UpToDate, and PsycINFO databases and three Chinese databases (CNKI, CBM, and Wan Fang Data) to identify articles written in English or Chinese that were published until Feb 1, 2020. Randomized controlled trials were included if they evaluated the impact of PST on major depression disorder (MDD) in older adults. Two authors of this review independently selected the studies, assessed the risk of bias, and extracted the data from all the included studies. We calculated the standard mean differences (SMDs) with 95% confidence intervals (CIs) for continuous data. We assessed heterogeneity using the I2 statistic. RESULTS: Ten studies with a total of 892 participants met the inclusion criteria. Subgroup analyses and quality ratings were performed. After problem-solving therapy, the depression scores in the intervention group were significantly lower than those in the control group (SMD = - 1.06, 95% CI - 1.52 to - 0.61, p < 0.05; I2 = 88.4%). DISCUSSION: Compared with waitlist (WL), PST has a significant effect on elderly patients with depression, but we cannot rank the therapeutic effects of all the treatment methods used for MDD. CONCLUSIONS: Our meta-analysis and systematic review suggest that problem-solving therapy may be an effective approach to improve major depressive disorders in older adults.

3.
Polymers (Basel) ; 11(6)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31159508

RESUMO

Polystyrene-based polyHIPE (polymerized high internal phase emulsion) materials were prepared by the copolymerization of styrene and divinylbenzene in the continuous phase of a HIPE. The resultant polyHIPE materials were found to have an open-cellular morphology and high porosity, and the polyHIPE structure could be well adjusted by varying the water/oil (W/O) ratio and the amount of emulsifier in the HIPE. Cell culture results showed that the resultant polyHIPE materials, which exhibited larger voids and connected windows as well as high porosity, could promote cell proliferation on the 3D scaffold. A 3D cell cytotoxicity evaluation system was constructed with the polystyrene-based polyHIPE materials as scaffolds and the cigarette smoke cytotoxicity was evaluated. Results showed that the smoke cytotoxicity against A549 cells is much lower in the 3D cell platform compared to the traditional 2D system, showing the great potential of the polyHIPE scaffolds for 3D cell culture and the cytotoxic evaluation of cigarette smoke.

4.
Toxicol Mech Methods ; 29(7): 499-510, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050318

RESUMO

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is classified as a Group 1 human carcinogen. It is metabolically activated by P450 enzymes to intermediate methylate and pyridyloxobutylate DNA, resulting in the formation of DNA adduct that is critical for the carcinogenicity of NNK. To directly and objectively examine the DNA adduct formation profiles without the complexity of factors in vivo, in the present study, five kinds of methyl DNA adducts were first identified in the incubation model of NNK established with human lung epithelial cells (BEAS-2B). The level of methyl DNA adducts and metabolites of NNK were quantitatively analyzed, respectively. With the increase of exposure time and dose, the level of methyl DNA adducts and metabolites increased. Furthermore, with the changes of the activity of P450 enzymes, which is the main enzyme regulating the α-hydroxylation of NNK, we found the levels of both methyl adducts and metabolites formed via α-hydroxylation in experimental groups showed the same trend compared with those in control group, while the metabolites formed via other pathways changed in the opposite trend. The result proves that the methyl adducts induced by NNK generate via α-hydroxylation pathway in BEAS-2B cells.


Assuntos
Carcinógenos/toxicidade , Adutos de DNA/metabolismo , Metilação de DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nitrosaminas/toxicidade , Carcinógenos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sistema Enzimático do Citocromo P-450 , Relação Dose-Resposta a Droga , Células Epiteliais/enzimologia , Células Epiteliais/metabolismo , Humanos , Hidroxilação , Pulmão/enzimologia , Pulmão/metabolismo , Nitrosaminas/metabolismo
5.
Entropy (Basel) ; 21(7)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-33267340

RESUMO

In this paper, we present a new secrecy-enhancing scheme for the spatial modulation (SM) system, by considering imperfect channel state information (CSI). In the proposed scheme, two antennas are activated at the same time. One of the activated antennas transmits information symbols along with artificial noise (AN) optimized under the imperfect CSI condition. On the other hand, the other activated antenna transmits another AN sequence. Because the AN are generated by exploiting the imperfect CSI of the legitimate channel, they can only be canceled at the legitimate receiver, while the passive eavesdropper will suffer from interference. We derive the secrecy rate of the proposed scheme in order to estimate the performance. The numerical results demonstrated in this paper verify that the proposed scheme can achieve a better secrecy rate compared to the conventional scheme at the same effective data rate.

6.
Curr Pharm Biotechnol ; 19(5): 428-437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29956625

RESUMO

BACKGROUND: The aim of this study was to investigate anti-apoptotic effects of luteolin on angiotensin II-stimulated murine peritoneal macrophages and to explore its mechanisms. METHODS AND RESULTS: The viability and cytotoxicity of murine peritoneal macrophages were assessed using the Cell Counting Kit-8 assay and measuring lactate dehydrogenase levels, respectively. Apoptotic rates were determined using Annexin V/propidium iodide staining. Protein expression was examined by western blotting, and markers of macrophage phenotypes were analyzed by flow cytometry and ELISA. Luteolin decreased the apoptotic rate of angiotensin II-stimulated macrophages. This effect was associated with increased Bcl-2 and caspase-3 levels as well as decreased Bax and cleaved caspase-3 levels. Additionally, luteolin reduced the expression of M1 macrophage phenotype markers (IL-6, TNF-α, iNOS, CD16/32) and increased the expression of M2 macrophage phenotype markers (Dectin-1, IL-10, Arg-1, CD206). Moreover, luteolin blocked Akt phosphorylation on residues 308 and 473, which were up-regulated in presence of angiotensin II. The effects of luteolin were similar to those of LY294002, a specific PI3K/Akt pathway inhibitor. CONCLUSIONS: These results indicated that luteolin has anti-apoptotic effects on angiotensin II-stimulated macrophages via macrophage polarization, which might be associated with PI3K/Akt signaling.


Assuntos
Angiotensina II/farmacologia , Apoptose/efeitos dos fármacos , Luteolina/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Polaridade Celular , Feminino , Macrófagos Peritoneais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
7.
Front Pharmacol ; 8: 692, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29056912

RESUMO

Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut in vitro and in vivo. Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration.

8.
Int J Immunopathol Pharmacol ; 30(3): 315-321, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28627972

RESUMO

Increasing evidence has demonstrated that the secretion of cytokines may be associated with cigarette smoke-induced immunomodulatory effects, but a comprehensive analysis of the cytokine profile for cigarette smoke condensate (CSC) exposure is lacking. The aims of this study were to (1) examine the release of 20 cytokines induced by CSC from 12 brands of cigarettes in macrophages cells (Ana-1) and (2) to investigate the general characteristics of the immunomodulatory effects of CSC. Luminex technology was used to simultaneously determine the levels of 20 cytokines (interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), keratinocyte-derived Chemokine (KC), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), induced protein 10 (IP-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), monkine inducible by γ interferon (MIG), and fibroblast growth factor (FGF)-basic) in the supernatants from Ana-1 cells treated with the CSC. The results showed that the release of eight cytokines was altered (IL-5, IL-6, IL-12, TNF-α, VEGF, IP-10, MCP-1, and MIP-1α) compared with the control. These cytokines fall into two major subtypes: proinflammatory cytokines, including IL-5, IL-6, IL-12, TNF-α, and VEGF, and chemokines, including IP-10, MCP-1, and MIP-1α. Compared with control, the remaining 12 cytokines were not significantly affected by CSC from the 12 brands of cigarettes. As a general characteristic, CSC exerts potently suppressive immunomodulatory effects on cytokine production of Ana-1 cells. Proinflammatory cytokines and chemokines may account for or contribute to the immunosuppressive properties of CSC.


Assuntos
Citocinas/metabolismo , Fatores Imunológicos/toxicidade , Macrófagos/efeitos dos fármacos , Fumaça/efeitos adversos , Produtos do Tabaco/efeitos adversos , Animais , Linhagem Celular , Macrófagos/metabolismo , Camundongos , Tabaco
9.
J Agric Food Chem ; 63(2): 569-77, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25536026

RESUMO

A new acidic polysaccharide (PLP) was isolated and characterized from Plantago asiatic L. seeds by hot alkali extraction and chromatographic purification using DEAE cellulose and Sephacryl S-400 columns. PLP has a molecular weight of 1.15 × 10(6) Da, and a monosaccharide composition of xylose (Xyl), arabinose (Ara), glucuronic acid (GlcA), and galactose (Gal) in a molar ratio of 18.8:7.2:6.1:1. The results of methylation analysis, FT-IR, and 1D and 2D NMR indicated that PLP was a highly branched heteroxylan of ß-1,4-linked Xylp backbone with three α-GlcAp-(1→3)-Araf attached to the O-3 position and one α-T-linked-GlcAp and one α-Araf-(1→5)-Araf attached to the O-2 position every eight monosaccharide residues. PLP exhibited scavenging abilities against hydroxyl, peroxyl anion, and DPPH radicals in vitro and showed significant binding capacities against cholic and chenodeoxycholic acids, suggesting its possible cholesterol-lowering activity. The results demonstrated the potential use of PLP in functional foods and nutraceuticals.


Assuntos
Ácidos e Sais Biliares/química , Depuradores de Radicais Livres/química , Extratos Vegetais/química , Plantago/química , Polissacarídeos/química , Sequência de Carboidratos , Depuradores de Radicais Livres/isolamento & purificação , Dados de Sequência Molecular , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Sementes/química , Espectroscopia de Infravermelho com Transformada de Fourier
10.
J Chromatogr A ; 1369: 170-80, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25441084

RESUMO

Supermacroporous poly(methacrylic acid-butyl methacrylate-ethylene glycol dimethacrylate) monoliths with the pore size up to 5-10 µm were successfully prepared in a ternary polymeric porogens utilizing viscoelastic effect. High concentration (over 20 mg/mL) of polystyrene (PS) in porogen was used to achieve the desirable characteristics of the monolithic capillary. Modification of the co-porogen composition, i.e., the content of dimethyl sulfoxide and isooctane, enabled tailoring of the supermacropore structure with a wide range of pore size. The effects of the amount of polymer porogen and molecular weights of PS on the formation of supermacropore were also studied. In preliminary applications, the separations of alkyl phenones and alkylbenzenes were achieved on the supermacropore columns using a mode of capillary electrochromatography. The study demonstrated successfully the ability of polymer porogen to form supermacropore monolith via viscoelastic phase separation.


Assuntos
Eletrocromatografia Capilar/métodos , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Cromatografia Líquida de Alta Pressão , Elasticidade , Peso Molecular , Porosidade , Reprodutibilidade dos Testes , Viscosidade
11.
J Agric Food Chem ; 62(17): 3783-90, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24712394

RESUMO

A novel polysaccharide (GPP-S), with a molecular mass of 1.2 × 10(6) Da, was isolated from the tetraploid Gynostemma pentaphyllum Makino by alkali extraction followed by purifications using DEAE and Sephacryl S-400 column chromatographies. The monosaccharide composition of GPP-S was determined as rhamnose, arabinose, glucose, and galactose with a molar ratio of 1.00:3.72:19.49:7.82. The structural analysis suggested that the backbone of GPP-S is (1→4)-linked-glucose and (1→6)-linked-galactose with a (1→4,6)-linked-glucose branch every six monosaccharide residues. The terminals were 1-)-α-arabinose, glucuronic acid, and other monosaccharides. GPP-S exhibited scavenging capacities against hydroxyl, peroxyl, and DPPH(•) radicals in vitro. GPP-S also had inhibitory activities on IL-1ß, IL-6, and COX-2 gene expressions in RAW 264.7 mouse macrophage cells. These results suggested that GPP-S could be developed as a bioactive ingredient for functional foods and dietary supplements.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Gynostemma/química , Extratos Vegetais/química , Polissacarídeos/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Gynostemma/genética , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Tetraploidia
12.
Exp Toxicol Pathol ; 66(1): 27-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23972641

RESUMO

An in vitro whole smoke (WS) exposure method was established to evaluate the toxicological effects of fresh cigarette smoke using the VITROCELL(®) system associated with the neutral red uptake (NRU) cytotoxicity assay. The VITROCELL(®) system is a newly representative culture and exposure system for in vitro studies of gases or complex mixtures. The impacts of two factors on cytotoxicity measurements of cigarette smoke were investigated using this WS exposure system. The factors include synthetic air exposure and optimal time to perform the NRU assay after smoke exposure. Results showed that synthetic air exposure used in the system did not significantly alter cell survival; 24h after smoke exposure appeared to be an optimal time-point to assess the cytotoxicity of cigarette smoke. A clear dose-response relationship between smoke exposure and cell viability was demonstrated using this system, and the evaluation method was sensitive to distinguish the differences in smoke-induced cytotoxic effects from different cigarettes. In addition, we tried converting the values of EC50 from WS exposure testing into the values in unit used in total particulate matter (TPM) testing for a purpose of comparison, and the data indicate that the cytotoxicity of smoke measured by WS exposure is greater than that measured by TPM exposure.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Fumaça/efeitos adversos , Fumar/efeitos adversos , Testes de Toxicidade/instrumentação , Testes de Toxicidade/métodos , Animais , Células CHO , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga
13.
Toxicol Mech Methods ; 23(4): 240-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23193988

RESUMO

In vitro cytotoxicity assays can be used to evaluate potential toxicological effects of tobacco products. Total particulate matter (TPM) from mainstream cigarette smoke trapped by a Cambridge filter is used widely for biological evaluation of smoke. This study compared neutral red uptake (NRU), lactate dehydrogenase (LDH) activity and WST-1 assays for assessing the cytotoxicity of TPM, and evaluated the sensitivity of Chinese hamster ovary (CHO) cells and human lung adenocarcinoma epithelial cell line (A549 cells) to TPM-induced cytotoxic effects. The results indicate that NRU and WST-1 assays are preferable to LDH activity assay for assessing the TPM-induced cytotoxicity, and NRU assay might be more sensitive than WST-1 assay. The cytotoxicity of 3R4F reference cigarettes and two commercial brands of cigarettes were tested by NRU assay in CHO and A549 cells. The results showed that EC50 values in CHO cells treated with TPM were lower than EC50 values in A549 cells, indicating CHO cells are more sensitive to TPM-induced cytotoxic effects than A549 cells.


Assuntos
Bioensaio/métodos , Material Particulado/toxicidade , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Células CHO , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Humanos , Fatores de Tempo
14.
Food Chem Toxicol ; 50(3-4): 545-51, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22198610

RESUMO

The purpose of this study was to evaluate the effects of test material format and smoking regimens on comparative toxicity testing of cigarette smoke. Total particulate matter (TPM) or whole smoke (WS) generated from three test cigarettes under International Organization for Standardization (ISO) or Health Canada Intensive (HCI) regimens were assessed for cytotoxicity using the neutral red uptake (NRU) cytotoxicity assay. Under both ISO and HCI regimens, the relative differences of cytotoxicity among the test cigarettes indicated by the EC50 values in WS were significantly higher than those in TPM. For TPM testing, cytotoxicity was decreased going from ISO regimen to HCI regimen, consistent with the reported reductions of toxicant output on a per unit of TPM basis under the HCI regimen. For WS, cytotoxicity increased for the two lower TPM cigarettes, and decreased for the higher TPM cigarette going from HCI regimen to ISO regimen. Results from this study demonstrated WS should be the preferable test material format for smoke toxicity testing whenever possible. Intensive smoking regimens, such as HCI, are less likely to underestimate smoke toxicant intakes by smokers, and should be included in the comparative toxicological testing strategy.


Assuntos
Fumar , Animais , Células CHO , Cricetinae , Cricetulus , Humanos , Tabaco
15.
Mol Cancer Ther ; 10(8): 1375-84, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21653685

RESUMO

Certain glycolipid antigens for natural killer T (NKT) cells can direct the overall cytokine balance of the immune response. However, the molecular mechanism of Th1- or Th2-biased cytokine secretion by NKT cells is still unknown. Previously, we synthesized isoglobotrihexosylceramide (iGb3) analogues by introducing a hydroxyl group at C4 on the ceramide portion of iGb3 to produce 4-HO-iGb3 or to further deoxylation on the terminal galactose to produce 4'''-dh-iGb3. Both modified iGb3, especially 4'''-dh-iGb3, stimulated more IFN-γ production by hepatic NKT cells, and thus elicited preferential Th1 responses. Here, we found that 4'''-dh-iGb3-loaded bone marrow-derived dendritic cells (DC) could significantly inhibit growth of subcutaneous melanoma and suppress lung metastasis in C57BL/6 mice compared with unmodified iGb3-loaded DCs. In investigating the mechanisms of this improved activity, we found that 4'''-dh-iGb3 stimulation increased STAT1 signaling by NKT cells, whereas the phosphorylation of Th2 type cytokine-associated transcription factor STAT6 signaling was not affected. Analysis of the structures of iGb3 and 4'''-dh-iGb3 revealed that 4'''-dh-iGb3 provides greater stability and affinity between glycolipid and CD1d or NKT TCR complex than iGb3. Thus, 4'''-dh-iGb3 can improve the antitumor effects of a DC-based vaccine possibly by stabilizing the CD1d/glycolipid/TCR complex and stimulating IFN-γ signaling of NKT cells. Furthermore, chemical modification of iGb3 can elicit Th1-biased responses by NKT cells, and 4'''-dh-iGb3 combined with a DC vaccine may serve as a potent new NKT-based therapy against tumors and infectious diseases.


Assuntos
Antineoplásicos/farmacologia , Globosídeos/farmacologia , Melanoma Experimental/metabolismo , Triexosilceramidas/farmacologia , Animais , Antígenos CD1d/química , Antígenos CD1d/metabolismo , Antineoplásicos/química , Sítios de Ligação , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Globosídeos/química , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Metástase Neoplásica , Ligação Proteica , Receptores de Antígenos de Linfócitos T alfa-beta/química , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Fator de Transcrição STAT1/metabolismo , Proteínas com Domínio T/metabolismo , Triexosilceramidas/química
16.
Int Immunopharmacol ; 8(5): 645-53, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18387506

RESUMO

Isoglobotrihexosylceramide (iGb3) has been identified as an endogenous ligand recognized by NKT cells; however, it is a weak agonist compared to the exogenous alpha-galactosylceramide. Modification of the structure of iGb3 might improve its stimulatory activity. In this study, we assessed the stimulating activity of chemically-modified iGb3 analogues on murine hepatic NKT cells. We analyzed the percentage of IFN-gamma- or IL-4-producing cells in hepatic iNKT cell population and found that two chemically-modified iGb3 analogues, especially 4'''-dh-iGb3, induced significantly greater intracellular IFN-gamma+ NKT cells in liver by flow cytometry. In vivo experiments also showed that 4-HO-iGb3 and 4'''-dh-iGb3 are selectively strong inducer for rapid serum IFN-gamma production compared with unmodified iGb3. Comparing the structure of iGb3 and its two iGb3 analogues, 4-HO-iGb3 has an extra hydroxy group on C4, suggesting that the additional hydroxy group of phytosphingosine might augment the stability of the CD1d/glycoceramide complex forming and thereby possibly promote IFN-gamma producing. By further modifying the polysaccharide of glycolipid as did in 4'''-dh-iGb3, we found that 4'''-dh-iGb3 elicited more Th1-biased responses than iGb3 and 4-HO-iGb3. This modification might more strongly strengthen the affinity of the TCR/glycoceramide complex and ultimately polarize iNKT cells to release more Th1 cytokines. Our data suggests that a combination modification on both polysaccharide and sphingosine chain of iGb3 elicits preferential Th1-biased responses.


Assuntos
Adjuvantes Imunológicos , Globosídeos/farmacologia , Interferon gama/biossíntese , Células Matadoras Naturais/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Triexosilceramidas/farmacologia , Animais , Linhagem Celular , Citocinas/sangue , Citometria de Fluxo , Globosídeos/química , Células Matadoras Naturais/efeitos dos fármacos , Fígado/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Relação Estrutura-Atividade , Triexosilceramidas/química
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