Amounts Of IL-6 Research Articles

Electropolymerization of pyrrole in ionic liquid microemulsion

AbstractThe direct electropolymerization of pyrrole in [BMIM]PF6 microemulsion was investigated for the first time. The H2O/TX‐100/[BMIM]PF6 (W/IL), bicontinuous (BC), [BMIM]PF6/TX‐100/H2O (IL/W) subregions can be used as electrolytes for pyrrole electropolymerization. The use of IL microemulsion remarkably reduces the amount of IL. Furthermore, electrochemical measurements indicated that W/IL microemulsion was the optimal medium and its polymerization rate was the fastest. Compared with molecular solvent system (0.25 mol L−1 [BMIM]PF6/acetonitrile) and neat [BMIM]PF6, the resultant films electrodeposited in W/IL microemulsion possessed excellent electrochemical activity and uniform morphology. All the results indicated that the H2O/TX‐100/[BMIM]PF6 microemulsion as electrolyte medium is the most suitable for electropolymerization of pyrrole. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Tissue-Specific Expression of Splice Variants of Human IL-4 and IL-6 Gene mRNA

The spectrum of alternatively spliced IL-4 and IL-6 gene mRNA was studied in peripheral blood mononuclears from healthy donors and in human fetal tissues. It was found that the expression of alternatively spliced IL-4 and IL-6 gene mRNA in fetal tissues is tissue specific and that hemopoiesis- and immunopoiesis-related tissues differ by the amount of IL-4 and IL-4δ2 mRNA. An mRNA variant IL-4alt3 carrying partial exon 3 deletion was for the first time identified in human mononuclear cells.

A Novel Method for Dye Removal: Ionic Liquid‐Based Dispersive Liquid–Liquid Extraction (IL‐DLLE)

AbstractA novel, simple, fast, and efficient ionic liquid‐based dispersive liquid–liquid extraction (IL‐DLLE) has been applied to extract and remove Congo Red (CR; a carcinogenic textile dye) from aqueous solutions. In this methodology a binary solution, containing the extraction solvent (1‐hexyl‐3‐methylimmidazolium bis(trifluormethylsulfonyl) imid) and a suitable disperser solvent, was rapidly injected into the water sample containing CR dye. Therewith, a cloudy solution was formed, and most of the dye molecules were extracted into fine IL droplets and removed from aqueous phase. The effects of pH, type, and amount of IL, initial concentration of the dye, type and volume of the dispersant, and concentrations of salt on the extraction of the dye were studied. Experimental surveys were also accomplished for recovery of the IL by applying a reverse dispersive liquid–liquid extraction using acidic stripping solutions.

Effects of r - HuEPO on expression of NF - κB and IκB in focal cerebral ischemia/reperfusion in rats

Objective To explore the function of NF - κB and IκB in the neuroprotection of EPO on inflammatory injury induced by cerebral focal ischemia/reperfusion in rats.Method Thread embolism was performed to establish cerebral ischmia/reperfusion model in rats.Immunohistochemistry and Western blot were employed to determine the expression of NF - κB and IκB in the ischemic context,respectively.The amount of IL - 1β protein was detected by ELISA.Results Compared with sham,the amount of IL - 1β protein was significantly induced in ischemic tissue.The expression of IL - 1β was increased to ( 86.2 ± 25.2) pg/ml and ( 867.2 ± 74.3 ) pg/ml at 3 h and 24 h of I/R ( P ＜ 0.01 ).The high level of IL - 1β expression was continued after 72 h I/R we observed.The administration of EPO significantly reversed the IL -1β expression induced by I/R at 3 h,6 h,12 h and 24 h.Compared with IL- 1β levels at different time points in I/R group,the amount of IL - 1β protein in EPO group decreased by 55％,33％,56％,50％ ( P ＜0.01 ).The expression and activation of NF - κB p65 was 4 - 13 folds higher in I/R groups in comparison with sham group at every time points.Interestingly,the expression of NF - κB p65 was remarkably decreased about 33％ ～40％ ( P ＜0.01 ) in EPO group compared with L/R group.Interestingly,Western blot showed that the amount of IκBαt inhibited by I/R was induced by the administration of EPO after I/R.The level of IKB increased by 11％,34％,83％,40％,23％,20％ at every time point.Conclusions EPO may be a protective molecule by inhibiting NF- κB/IκB signalling pathway,decreasing the synthasis and secretion of IL- 1β. Key words: Erythropoietin, recombinant; Brain ischemia; Reperfusion; NF - kappa B; Inhibitory κB

Tr17: A Unique Subset of T Regulatory Cells with Distinct Molecular and Functional Properties

Abstract 1116 A major challenge of the immune system is to fight pathogens and abnormal cell growth while preserving immune tolerance to self-antigen. Active immune suppression by T regulatory (Treg) cells is one of the mechanisms that maintain peripheral T cell tolerance and homeostasis. Recent findings suggest that Treg cells are heterogeneous in functions and phenotypes. Moreover, Treg cells might not be at a terminal stage of differentiation but rather display a significant degree of plasticity particularly under inflammatory conditions. We have previously determined that co-culture of conventional CD4+ T cells and Treg cells in the presence of antigen presenting cells (APC) during T cell receptor mediated stimulation, induced Treg cells producing IL-17 (thereafter named Tr17 cells). IL-1β and IL-2, endogenous products of the co-culture, were essential for the conversion of Treg cells into Tr17 cells. In the present study we sought to identify the phenotypic and functional properties of Tr17 cells. First, we examined the role of IL-2 and IL-1β in the generation of Tr17 cells. Treg cells from Foxp3.GFP knock-in mice were stimulated with anti-CD3 and anti-CD28 in the presence of IL-1β-plus-IL-2. A fraction of purified Foxp3+ Treg cells produced significant amounts of IL-17 as determined by ELISA and by intracellular cytokine staining. Very few Tr17 cells were observed during T cell activation in the absence of either IL-1β or IL-2, suggesting that the combination of IL-1β and IL-2 was required for the development of Tr17 cells. Compared to IL-17-Treg, Tr17 cells expressed increased levels of RORγt, the key transcription factor for Th17 cell differentiation. Expression of CCR6 is regulated by RORγt and is one of the features of Th17 cells. To determine whether expression of CCR6+ correlates with the ability of Treg to produce IL-17, we depleted CCR6+ Treg from Foxp3.GFP+ populations and examined the ability of the resulting Treg to produce IL-17. Depletion of CCR6+ Treg resulted in significantly reduced IL-17 production compared with total Foxp3+ Treg cells, suggesting that CCR6+ Treg cells might represent Tr17 cells. Because inducible costimulatory molecule (ICOS) was recently shown to be critical for the differentiation, expansion and function of Th17 cells we examined its role in Tr17 cells. We determined that Tr17 cells expressed strikingly elevated levels of ICOS compared to IL-17− Treg obtained from the same cultures. These results indicate that Tr17 cells acquire phenotypic properties of Th17 cells, which involve RORγt-dependent and independent mechanisms. To determine whether besides obtaining features of Th17 cells, Tr17 cells also retained properties of Treg we first assessed the expression of Foxp3. Compared to IL-17− Treg, Tr17 cells displayed lower levels of Foxp3. However, expression of CTLA-4 and GITR, two other signature makers of Treg cells, was comparable in IL-17− Treg and Tr17 cells. Similarly, both Tr17 and IL-17− Treg cells displayed suppression capacity. Taken together, our results suggest that Tr17 is a unique subset of Treg cells that is differentiated under inflammatory conditions and displays combined phenotypic and functional properties of both Th17 and Treg cells. Because Treg use canonical CD4+ effector cell-associated transcription factors to regulate the immune responses of lineage-specific effectors, our findings suggest that Tr17 cells may have a unique role in regulating Th17-mediated inflammatory responses. Disclosures: No relevant conflicts of interest to declare.

Asymmetric lactic acid esterification with biocatalysts in ionic liquid

Biodegradability and environmentally friendly technologies recently came into prominence; this is the reason why we assayed to develop a new “green” technology for L-lactic-acid (LLA) production. Racemic lactic acid (rLA) mixture produced by chemical industry is difficult to handle. The product of esterification with low carbon chain alcohols has higher volatility than lactic acid (LA) itself, therefore it can be more effectively separated. Our reactions were carried out with biocatalysts (enzymes) — some of them prefer reactionswith L-enantiomer — result in enantioselective esterification. After LLA ester production the hydrolysis leads to separated LLA, which is the starting material of a biodegradable plastic. Our aim was to achieve enantioselectivity in phosphonium-type ionic liquid solvents by the optimization of several parameters, such as temperature, substrate molar ratio, amount of IL, water content. Reasonable results were achieved with three types (Candida antarctica, Candida rugosa, AMANO PS-IM) of lipases. The use of enzymes and ionic liquids can make the technology “greener”, where an ingredient of a biodegradable plastic can be produced. The toxic heavy metals or hazardous acids can be replaced by biocatalyst (enzymes). These intermediates are re-usable, and they work at lower temperature, than conventional catalysts, thus the operational costs can be reduced. Ionic liquids — compared with conventional organic solvents — have insignificant vapour pressure, they are non-flammable and re-usable after a purification process, furthermore they can betailor made for a certain application. It is not negligible that the structure affects the environmental features like biodegradability or toxicity. The high lactic acid dissolving capacity is the reason why phosphonium-type ionic liquids were used. There are research teams, apply them for lactic acid extraction from fermentation broth.

Dietary flaxseed oil decreases interleukin‐1 and alpha‐smooth muscle actin in a rat bleomycin‐induced fibrosis model

Dietary fish oil, containing long chain ω‐3 fatty acids, has been previously found to protect against monocrotaline‐induced pulmonary fibrosis. This study is investigated the effects of ω‐3 fatty acids‐enriched flaxseed oil on bleomycin‐induced pulmonary fibrosis. Forty‐two Sprague‐Dawley rats were assigned into seven groups with various doses of flaxseed oil at 0, 2.5, 5, 7.5, 10, 12.5, and 15% (w/w) in the diet for one month prior to treating with bleomycin at 8 U/ kg oropharyngeally. Two weeks after bleomycin treatment, the rats were sacrificed and three proteins including TGF‐β, IL‐1, and α‐Smooth Muscle Actin (α‐SMA), commonly associated with fibrotic inflammation in the lung, were examined by Western blot. The amount of IL‐1 and α‐SMA decreased significantly as the amount of ω‐3 fatty acids increased, whereas TGF‐β did not change significantly. In addition, fatty acid profiles from the liver and lung tissues were analyzed by lipidomics, resulting an increased ratio of ω‐3:ω‐6 fatty acids in both tissues as the amount of flaxseed oil increased. These results indicated that the ω‐3 fatty acids in flaxseed oil inhibited the formation of pulmonary fibrosis in a dose‐dependent manner via anti‐inflammatory mechanisms, which appears associated with the modulated fatty acid composition in the tissues.

Effect of 1-butyl-3-methylimidazolium nitrate on separation properties of polymer/AgNO3 membranes for propylene/propane mixtures: Comparison between poly(2-ethyl-2-oxazoline) and poly(ethylene oxide)

A previous study showed that ionic liquids enable AgNO3, which is not readily reduced to silver nanoparticles in the solid state, to be an active olefin carrier in silver polymer electrolyte membranes. We report the effects of an ionic liquid, i.e. 1-butyl-3-methylimidazolium nitrate (BMIM+NO3−), on the separation properties of polymer/AgNO3 complex membranes for propylene/propane mixtures. Interestingly, the change in membrane separation properties with the ionic liquid concentration was completely different between poly(2-ethyl-2-oxazoline) (POZ) and poly(ethylene oxide) (PEO). In the POZ/AgNO3 complex membranes, both the selectivity of propylene/propane and the mixed gas permeance increased up to a 0.1 mole ratio of ionic liquid, after which they decreased. The enhancement of the membrane performance results from an increase in the silver ion activity, whereas the decrease was attributed to the barrier effect of large amounts of IL and less effectiveness of IL in controlling the ionic interactions. On the other hand, in the PEO/AgNO3 membranes, the selectivity increased with increasing ionic liquid, whereas the mixed gas permeance decreased. The increase in selectivity comes from the enhanced silver ion activity, whereas the decrease in permeance was attributed to the decrease in interfacial voids in the membranes.

Effects of a micromolecular compound target to CD4-J2 on lymphocytes of mouse after corneal allograft

目的 探讨小分子化合物J2对异基因角膜移植小鼠淋巴细胞的影响.方法 建立小鼠角膜移植模型,随机分为A、B、C、D 4个组.A组为空白对照组3只BALB/c小鼠,B、C、D组各11只鼠,均取右眼行C57BL/6-BALB/c同种异体角膜移植术,自手术当日开始腹腔注射给药,B组给予不含药物的安慰剂,C组给予环孢素A(CsA)10mg/kg,D组给予J2 15mg/kg,每日1次,连续给药12d.给药后7d,取大鼠脾细胞给予刀豆蛋白(ConA)刺激细胞增生,采用ELISA法测定细胞上清液中白细胞介素-2(IL-2)及IL-4的含量,比较各组细胞增生指数及细胞因子含量.结果 B组角膜植片平均存活时间为(18.88±4.19)d,C组、D组发生排斥时间分别为(35.13±5.74)d、(33.62±6.80)d,明显延迟,与B组比较差异均有统计学意义(q=9.17,P＜0.01;q=8.33,P=0.00),而C组与D组比较差异无统计学意义(q=0.85,P=0.60).ConA刺激角膜移植后小鼠脾细胞增生,各组小鼠脾细胞的增生指数差异无统计学意义(F=3.729,P=0.061).异基因小鼠角膜移植后3周左右小鼠脾细胞中IL-2和IL-4的含量无明显变化.应用ConA刺激后ELISA法检测结果表明,角膜移植小鼠脾细胞分泌IL-2明显增多,J2可抑制ConA诱导的IL-2分泌增加.结论 J2可能通过抑制CD4+ T淋巴细胞而抑制角膜排斥反应的发生;J2能够明显抑制ConA刺激角膜移植后小鼠脾细胞的增生及Th1细胞因子的产生。

Behaviors of ionic liquids in the phase transfer of aqueous metal nanoparticles

To understand why ionic liquids are efficient solvents for the phase transfer of metal nanoparticles, we added a small amount of ILs to dichloromethane and studied the behaviors of ILs in the phase transfer. The proposed mechanism of phase transfer is the formation of a hydrophobic ion-pair between the cation of the stabilizer on the particle surface and the anion of the ILs, which cause the change in the surface hydrophilic properties and facilitate the phase transfer of aqueous nanoparticles into an organic phase. This mechanism was supported by NMR, FT-IR, XPS and ESI-MS. Furthermore, we investigated the effects of parameters on the phase transfer and found that phase-transferring efficiency increases with the extraction time and the concentration and hydrophobicity of the ILs. The results indicate that ILs play the roles of phase-transfer agents and solvents in the phase transfer of aqueous metal nanoparticles with ILs.

Electrical conductivity studies on composite polymer electrolyte based on ionic liquid

PEO: IL(1-ethyl-3-methylimidazolium Tosylate) and (PEO: IL) + xAl2O3 polymer composite films have been obtained by (a) hot press and (b) solution cast techniques. The films prepared by hot press techniques give higher conductivity than their corresponding solution-casted samples. The PEO: IL polymer films conductivity has been found to increase with the amount of IL in PEO polymer matrix at a given temperature. The temperature dependence conductivity of PEO: IL films have been studied and discussed for the films prepared by two preparatory methods (a) hot press and (b) solution cast. The temperature dependence of conductivity exhibited an Arrhenius-type thermally activated behaviour. The ceramic filler Al2O3 concentration-dependent conductivity of PEO + IL (20 wt.%) film shows two conductivity maxima at 2 and 10 wt.%, respectively, which has been explained on the basis of double percolation threshold model.

Dendritic Cells Generated in Clinical Grade Bags Strongly Differ in Immune Functionality When Compared With Classical DCs Generated in Plates

Mature dendritic cells (DCs) represent, by far, the most potent antigen-presenting cells. The development of clinical grade techniques to produce them in large numbers has rendered possible their use in clinical trials. It is therefore crucial to assess the DCs characteristics according to the methodology used to generate them, to improve the comparison and standardization of these trials. We thus compared DCs generated and matured in culture plates (pla-DCs) or in clinical grade bags (bag-DCs) by analyzing, their secretion of bioactive interleukin (IL)-12 and their capacity to induce in-vitro primary responses. We also used several molecular techniques to better characterize the functional differences between the 2 type of DCs. Mature bag-DCs displayed a mature phenotype, but did not secrete significant amounts of IL-12 and failed to initiate primary immune responses. Molecular analyses performed on immature bag-DCs showed them already engaged in a particular maturation process (early activation of nuclear factor kappa B and beta-catenin). Using microarrays, we found underexpression of receptors for the maturation cocktail in bag-DCs. In mature bag-DCs, we found crucial genes (IL-12, chemokines, and costimulatory and adhesion molecules) down-regulated. Electrophoertic mobility shift assay and Western blots showed a normal activation profile in mature pla-DCs, but not in bag-DCs where the Mek/Erk pathway was still activated. Our results strongly suggest that differentiation of monocytes into DCs in bags generates immature DCs already engaged in an inefficient type of activation, with down-regulation of genes involved in response to the maturation cocktail. This results in mature DCs unable to induce T(H)1-type responses.

Abstract 4788: Modulation of T lymphocytes by tumor-released survivin

Abstract Introduction: The role of tumor infiltrating lymphocytes (TILs) in the progression of cancer has become an important area of research. Recent studies have shown that T lymphocytes within the tumor microenvironment have decreased activation and proliferation. Our lab has shown survivin is released from tumor cells within exosomes, and is capable of altering the phenotype of malignant cells. We hypothesize that this exosomally-released survivin prevent TIL activation and proliferation in T cell subsets and that Th2 type cytokines will be released in higher levels than Th1 cytokines. Methods: HeLa-S-WT cells that produce Flag-HA tagged survivin were growth in a bioreactor and survivin isolated from the media using Flag-HA tandem affinity purification. T lymphocytes from normal donors were cultured in control or survivin-containing media and activated with anti-CD28-anti-CD3 microbeads (32 ul/ml). Flow cytometric analysis of activation marker CD69 and the proliferation marker Ki-67 were performed at 24h and 6 days, respectively. Cytokine release was evaluated using a Cytokine Bead Array (BD Bioscience) for IFN-gamma, IL-2, IL-4 and IL-10. Results: CD69 expression was decreased significantly in CD8+ T cells after incubation with survivin (Control = 72 MFU, Treated = 57 MFU; p<0.05) while no significant change was seen in CD4+ T cells (Control = 65 MFU, Treated = 68 MFU). CD8+ T cells showed a significant reduction in Ki-67 expression after incubation with survivin when compared to controls (Control = 218 MFU, Treated = 139 MFU; p < 0.001), while CD4+ T cells showed little difference between control and treated groups (Control = 74 MFU, Treated = 81 MFU). Cells treated with survivin in activating conditions released higher amounts of IL-4 (Control = 4.8 pg/ml, Treated = 28.3 pg/ml) and decreased amounts of IFN-gamma (Control = 32.4 pg/ml, Treated = 16.9 pg/ml) compared to control activating conditions. IL-2 and IL-10 showed little difference between treatment groups. Conclusions: This data suggests that survivin in the tumor microenvironment is capable of negatively affecting cytotoxic T cell activation and proliferation. While survivin treatment does not affect the activation or proliferation of CD4+ subsets, the Th1: Th2 cytokine balance is altered when survivin is present. Thus, survivin in the tumor microenvironment could play a role in the suppression of immune surveillance by inhibiting the cytotoxic T cell response and preventing tumor death by increasing levels of Th2 cytokines and decreasing levels of Th1 cytokines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4788.

Abstract 2449: A novel humanized anti-IL-1beta antibody is highly effective at inhibiting IL-1 induced IL-6 production in myeloma patients in vitro

Abstract Background: IL-6 is a central myeloma growth factor and in vitro abnormal production of IL-1beta in the myeloma microenvironment stimulates the generation of paracrine IL-6. Mimicking in vitro observations, we have shown that responsive early stage myeloma patients at risk for progression to active myeloma who were treated with IL-1 inhibitors demonstrated decreases in the myeloma proliferative rate and C-reactive protein (IL-6 surrogate marker) leading to a chronic disease state with an improved progression free survival. In this study we investigated the effect of XOMA 052, a humanized anti-IL-1 antibody to inhibit stromal cell IL-6 production induced by either recombinant IL-1beta or supernatants generated from unsorted bone marrow cells from patients with smoldering multiple myeloma. Methods: Bone marrow stromal cells were incubated with varying concentrations of recombinant IL-1β (100, 10, 1, 0.1 pg/ml) in the absence or presence of anti-IL-1 antibody, anti-TNF antibody, or dexamethasone. In a similar fashion, supernatants from unsorted bone marrow cells from six patients with smoldering myeloma were co-cultured with bone marrow stromal cells and the effect of the humanized anti-IL-1β antibody was tested. Results: The anti-IL-1β antibody inhibited the IL-1 induced IL-6 production in vitro by > 85% at 100 pg/ml of IL-1 and > 90% at 10, 1, and 0.1 pg/ml of IL-1; specifically, using 10 pg/ml of IL-1, IL-6 production was inhibited from 149 down to 5.2 ng/ml in the presence of anti-IL-1 antibody. Anti-TNF antibody had minimal effect. At 10 pg/ml of IL-1 beta, a physiologically relevant amount of IL-1 in vitro in bone marrow samples from myeloma patients, the anti-IL-1 antibody was superior to dexamethasone at inhibition of IL-6 production. In in vitro testing of patient supernatants from unsorted bone marrow cells, three patients were high inducers and three patients low inducers of paracrine IL-6 production. The results demonstrate > 85% reduction of IL-6 production in all patients' samples tested. Importantly, the anti-IL-1β antibody was highly effective in samples from the three patients who were high inducers of paracrine IL-6 production (IL-6 production was inhibited from 191 down to 12 ng/ml; 157 to 13 ng/ml and 320 to 11 ng/ml). In comparison, the anti-TNF antibody had marginal effects. Conclusion: The humanized anti-IL-1beta antibody is highly effective in vitro at the inhibition of IL-6 generated by supernatant cultures from patients with early stage myeloma or by recombinant IL-1. Combination therapy with IL-1 inhibitors and apoptosis inducing agents may be useful in patients with active myeloma that have elevated IL-6 levels and a high growth rate at diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2449.

Induction of CD4+CD25+Foxp3+IL-10+ T Cells in HDM-Allergic Asthmatic Children with or without SIT

Background: Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-β₁, may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy. Methods: PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5–2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-γ and TGF-β₁in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay. Results: Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-β were lower and the amounts of IFN-γ were higher in the SIT group compared with the asthma group. Conclusion: There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4⁺CD25⁺Foxp3⁺ Treg cells.

Synthesis of dimethyl carbonate from ethylene carbonate and methanol using immobilized ionic liquid on amorphous silica

Ionic liquid immobilized on mesoporous amorphous silica was prepared from the coupling of 1-(triethoxysilylpropyl)-3- n-alkyl-imidazolium halides with tetraethyl orthosilicate (TEOS) through template-free condensation under strong acidic conditions. The immobilized 1- n-butyl-3-methyl imidazolium bromide ionic liquid on amorphous silica (BMImBr-AS) was characterized by EA, N 2 adsorption, FT-IR, 13C NMR and 29Si NMR. The immobilized amount of IL was 1.27 mmol/g-SiO 2 and surface area was 652 m 2/g with bimodal distribution of pores. The average pore diameter was 3.3 and 24.6 nm, respectively. The silica-supported ionic liquids were proved to be an effective heterogeneous catalyst for the synthesis of dimethyl carbonate (DMC) from transesterification of ethylene carbonate (EC) with methanol. High temperature, high carbon dioxide pressure, and longer reaction time were favorable for the reactivity of BMImBr-AS. The catalyst can be reused for the reaction up to three consecutive runs with a slight decrease of its catalytic activity.

Emerging from the shadows: Follicular helper T cells in autoimmunity

Emerging from the shadows: Follicular helper T cells in autoimmunity

Paradoxical Roles of IL-4 in Tumor Immunity

Interleukin (IL)-4 is a crucial cytokine in tumor immunology. In the initial murine experiments, IL-4 exhibited potent anti-tumor ability. Tumors genetically modified to produce IL-4 were rejected, while parental tumors grew progressively. Mice rejected IL-4-producing tumors got long-lasting anti-tumor immunity. The comparative study showed that IL-4 induced the most effective immune response among several cytokines in both prophylactic and therapeutic models. All of these indicate IL-4 has strong potential as a tumor therapy agent. However, contrary evidence indeed exists, and is becoming more and more abundant which shows IL-4 is a tumor-promoting molecule. IL-4 amounts are usually elevated in human cancer patients. IL-4 knockout mice are more resistant to tumor challenge than IL-4 competent mice. Furthermore, tumor cells of various histological origins often express increased levels of IL-4 receptor in comparison to their normal counterparts. By carefully examining presently available data, we found the effects of IL-4 in tumor immunity are closely related to its sources, expressing time and dose, as well as the molecular and cellular environments. In this mini-review, we concentrate on illustrating the paradoxical roles and underlying mechanisms of IL-4 in tumor immunity and try to understand how one molecule has opposite effects.

Peritumoral administration of granulocyte colony-stimulating factor induces an apoptotic response on a murine mammary adenocarcinoma

The aim of the present study was to evaluate the in vivo effect of granulocyte colony-stimulating factor (G-CSF) on LM3 murine mammary adenocarcinoma cells subcutaneously implanted in Balb/c mice as experimental models. We showed that the peritumoral administration of 100 μg/kg of G-CSF diminished tumor progression, while no cytokine effect on LM3 cell proliferation was observed in vitro. Histological examination of G-CSF-treated tumors revealed infiltration of neutrophils and mononuclear cells. Apoptotic cells were identified by TUNEL assays. Western blot analysis of tumor lysates showed that G-CSF treatment increased the amount of Fas-L, TRAIL and Bax proteins, whereas decreased the expression of procaspase 3 and Bcl-2. In addition, cytokine arrays showed an increment in the amount of IL-12, IL-13 and TNF-α. Our results suggest that the presence of G-CSF within tumor microenvironment would induce an immune response which eliminates tumor cells by apoptosis. Both death receptor and mitochondrial pathways would be involved in LM3 tumor cell death. We believe that the final local G-CSF concentration at the tumor site and each particular type of tumor should be carefully taken into account in order to evaluate the effect of the cytokine on tumor progression.

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

The cytokines IL-6, IL-1beta, TGF-beta, and IL-23 are considered to promote Th17 commitment. Langerhans cells (LC) represent DC in the outer skin layers of the epidermis, an environment extensively exposed to pathogenic attack. The question whether organ-resident DC like LC can evoke Th17 immune response is still open. Our results show that upon stimulation by bacterial agonists, epidermal LC and LC-like cells TLR2-dependently acquire the capacity to polarize Th17 cells. In Th17 cells, expression of retinoid orphan receptor gammabeta was detected. To clarify if IL-17(+)cells could arise per se by stimulated LC we did not repress Th1/Th2 driving pathways by antibodies inhibiting differentiation. In CD1c(+)/langerin(+) monocyte-derived LC-like cells (MoLC), macrophage-activating lipopeptide 2, and peptidoglycan (PGN) induced the release of the cytokines IL-6, IL-1beta, and IL-23. TGF-beta, a cytokine required for LC differentiation and survival, was found to be secreted constitutively. Anti-TLR2 inhibited secretion of IL-6, IL-1beta, and IL-23 by MoLC, while TGF-beta was unaffected. The amount of IL-17 and the ratio of IL-17 to IFN-gamma expression was higher in MoLC- than in monocyte-derived DC-cocultured Th cells. Anti-IL-1beta, -TGF-beta and -IL-23 decreased the induction of Th17 cells. Interestingly, blockage of TLR2 on PGN-stimulated MoLC prevented polarization of Th cells into Th17 cells. Thus, our findings indicate a role of TLR2 in eliciting Th17 immune responses in inflamed skin.