bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat
Authors: Kessel A , Toubi E , Pavlotzky E , Mogilner J , Coran A G , Lurie M , Karry R , Sukhotnik I 
Published: July 2010

SummaryRecent evidence suggests that lipopolysaccharide (LPS) endotoxaemia in a rat causes significant mucosal injury. Our objective was to determine the effects of glutamine (Gln) on Toll-like receptor 4 (TLR-4), myeloid differentiation factor 88 (Myd88) and tumour necrosis factor (TNF)-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following LPS endotoxaemia in a rat. For this purpose, male Sprague–Dawley rats were assigned randomly to one of three experimental groups of 10 rats each: (i) control rats underwent intraperitoneal (i.p.) injection of sterile saline once a day; (ii) rats were treated with LPS given i.p. once a day at a dose of 10 mg/kg for 48 h (two doses); and (iii) rats were pretreated with oral Gln given in drinking water (2%) 48 h before and following injection of LPS. Intestinal mucosal parameters, enterocyte proliferation and apoptosis were determined at death. TLR-4 and MyD88 mRNA expression was measured with reverse transcription–polymerase chain reaction (RT–PCR). TLR-4 and MyD88 protein expression were analysed by Western immunoblotting. We observed a statistically significant (P &lt; 0·05) decrease in mucosal weight, mucosal DNA and enterocyte proliferation and a significant increase in enterocyte apoptosis in rat intestine, following LPS administration. These changes were attenuated significantly by dietary Gln. Expression of TLR-4, MyD88 and TRAF6 mRNA in the mucosal ileum was significantly higher in LPS rats versus control rats (P = 0·0006, P = 0·0015, P = 0·03, respectively) as well as TLR-4 and MyD88 protein expression. The administration of Gln reduced significantly the expression of TLR-4, MyD88 and TRAF6 (P = 0·023, P = 0·014, P = 0·035, respectively) mRNA as well as TLR-4 and MyD88 protein expression in ileum compared to LPS animals. We did not find a significant change in the expression of TLR-4, MyD88 or TRAF6 in the jejunum of different groups. We conclude that treatment with Gln was associated with down-regulation of TLR-4, MyD88 and TRAF6 expression and concomitant decrease in intestinal mucosal injury caused by LPS endotoxaemia in a rat.
BDCA-1+, BDCA-2+ and BDCA-3+ dendritic cells in early human pregnancy decidua
Authors: Ban Y-L , Kong B-H , Qu X , Yang Q-F , Ma Y-Y 
Published: July 2010

SummaryDendritic cells (DCs) can acquire unique features or phenotypes in different tissue microenvironments and decide whether immunity or tolerance develops. DCs observed within the decidua have been implicated in pregnancy maintenance. However, the precise distribution of decidual DC subsets and their phenotypic characteristics are largely unknown. Using flow cytometry, we identified three DC subsets in normal human first-trimester decidua: BDCA-1+ CD19- CD14- myeloid DC type 1 (MDC1), BDCA-3+ CD14- myeloid DC type 2 (MDC2) and BDCA-2+ CD123+ plasmacytoid DC (PDC). The percentage of MDC1 to mononuclear cells in the decidua was similar to that in the peripheral blood controls. The percentage of MDC2 in the decidua was significantly higher than that in the peripheral blood controls, whereas the percentage of PDC was significantly lower. Both MDC1 and MDC2 subsets expressed human leucocyte antigen D-related, CD86 and CD80 at low levels, suggesting a characteristic of immature myeloid DCs. Immunoglobulin-like transcript 3, suggested to be involved in immune tolerance induction, was also expressed on decidual MDC1 and MDC2 subsets. In addition, as gestational age increased from 6 to 9 weeks, the numbers of MDC1 decreased but MDC2 increased significantly. This is the first study to demonstrate the presence of three previously unidentified BDCA-1+, BDCA-3+ and BDCA-2+ DC subsets in human decidua, these decidual DCs might play important role in the maintenance of pregnancy.
Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus
Authors: Lee C-S , Hu C-Y , Tsai H-F , Wu C-S , Hsieh S-L , Liu L-C , Hsu P-N 
Published: July 2010

Summary
Decoy receptor 3 (DcR3/TR6) is a decoy receptor for the Fas ligand (FasL) and can inhibit FasL-induced apoptosis. It has been reported recently that DcR3 can induce T cell activation via co-stimulation of T cells, suggesting that DcR3 may be involved in the pathophysiology of autoimmune diseases. This study aims to analyse the serum DcR3 in patients with systemic lupus erythematosus (SLE) and to investigate the role of DcR3 in the pathogenesis of SLE. Significantly elevated serum DcR3 was observed in SLE patients, and the mean serum DcR3 level was significantly higher for those with active disease [SLE disease activity index (SLEDAI) ≥ 10] compared with that in patients with inactive disease (SLEDAI &lt; 10). In addition to reducing activation-induced cell death in activated T cells via neutralization of the FasL, soluble DcR3–Fc enhanced T cell proliferation and increased interleukin-2 and interferon-γ production via co-stimulation of T cells. Moreover, enhanced T cell reactivity to DcR3-induced co-stimulation was demonstrated in lymphocytes from patients with SLE, suggesting the elevated serum DcR3 may associate with enhanced T cell activation in vivo. These findings are the first to demonstrate that serum DcR3 concentrations are increased in SLE patients, and this may imply a possible role of DcR3 in the pathogenesis of SLE via enhanced T cell hyperreactivity and reduced apoptosis in activated T cells.
Natural killer cells are required for accelerated type 1 diabetes driven by interferon-β
Authors: Alba A , Planas R , Clemente X , Carrillo J , Ampudia R , Puertas M-C , Pastor X , Tolosa E , Pujol-Borrell R , Verdaguer J , Vives-Pi M 
Published: July 2010

SummaryThe destruction of β cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-β in β cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-β mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-β transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of β cell-specific autoimmunity mediated by NK cells.
Interleukin-21 stimulates antigen uptake, protease activity, survival and induction of CD4+ T cell proliferation by murine macrophages
Authors: Rückert R , Bulfone-Paus S , Brandt K 
Published: July 2010

Summary
Interleukin (IL)-21 is a T cell-derived cytokine which uses a heterodimeric receptor, composed of the common γ-chain (CD132) and an IL-21Rα-chain. IL-21 activates lymphoid T and B cells, modulates antibody production but also suppresses maturation of myeloid dendritic cells; however, its role in the differentiation and function of other myeloid cells remains less clear. In this study we analysed IL-21/IL-21Rα effects on macrophage (MΦ) differentiation and function. MΦ could be generated readily from bone marrow with MΦ–colony-stimulating factor in the presence of IL-21 (designated IL-21MΦ) or from IL-21Rα–/– mice. IL-21Rα–/– mice had normal MΦ numbers, suggesting a non-essential role of both IL-21 and the IL-21Rα for MΦ generation. We could demonstrate that mature MΦ express the IL-21Rα and the common γ-chain. However, short-term IL-21 stimulation did not enhance MΦ proliferation but induced anti-apoptotic cell-cycle regulators p21waf1/p27Kip1 and expression of suppressors of cytokine signalling (SOCS)2/SOCS3. Moreover, IL-21 enhanced phagocytosis by MΦ via IL-21Rα signalling and supports protease activity and matrix metalloproteinase 12 expression. Stimulating MΦ with IL-21 enhanced their capacity to induce antigen-specific CD4+ T cell proliferation in dependence from the IL-21Rα, which was not the case for CD8+ T cells. Taken together, IL-21 plays a previously unrecognized role in modulating innate and acquired effector mechanisms of murine MΦ by linking these different functions to support CD4+ T cell-mediated immune responses.
AvirulantSalmonella typhimuriumstrains prevent food allergy in mice
Authors: Eigenmann P A , Asigbetse K E , Frossard C P 
Published: July 2010

SummaryOral tolerance to foods can be regulated by microorganisms in the gut lumen. We hypothesized that pretreatment with avirulent Salmonella typhimurium strains could prevent food allergy in mice. Mice were administered S. typhimurium PhoPc (STPhoPc) or S. typhimurium AroA prior to oral sensitization to β-lactoglobulin in the presence of cholera toxin. An oral antigen challenge after sensitization assessed antigen-induced anaphylaxis. Antigen-specific antibody titres were measured by enzyme-linked immunosorbent assay in the serum and enzyme-linked immunospot (ELISPOT) in the spleen, and cytokine-secreting cells were measured by ELISPOT in the Peyer's patches, lamina propria and epithelium cells. We showed first that S. typhimurium could up-regulate interleukin (IL)-12 and IL-10 secretion by gut T cells. Mice pretreated with STPhoPc had decreased anaphylaxis upon challenge, along with decreased immumoglobulin G1 (IgG1) and IgE antibody titres. Mice having received S. typhimurium AroA had partly decreased anaphylaxis as well as decreased serum IgG1 antibody titres in the serum, and increased serum IgA antibody titres. Antibody titres could be correlated with increased numbers of spleen and Peyer's patches antibody-producing cells. STPhoPc-treated mice showed significantly decreased anaphylaxis when compared with the control mice, while S. typhimurium AroA-pretreated mice had a similar immune response together with increased secretory IgA titres. Our experiments have proved a potential immunomodulatory protective effect by two avirulent S. typhimurium strains.
BeWo trophoblast cell susceptibility toToxoplasma gondiiis increased by interferon-γ, interleukin-10 and transforming growth factor-β1
Authors: Barbosa B F , Silva D A O , Costa I N , Mineo J R , Ferro E A V 
Published: July 2010

SummaryThe present study aimed to investigate BeWo trophoblast cell susceptibility to Toxoplasma gondii infection under stimulation with anti-inflammatory cytokines in comparison with HeLa cells. Both cell types were submitted to different treatments with recombinant cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-β1] or the respective antibodies (anti-IL-10 and anti-TGF-β) before and after T. gondii infection. The effect of interferon (IFN)-γ was also assessed alone or in combination with anti-inflammatory cytokines or the respective antibodies after the parasite infection. Cells were fixed, stained and parasites quantified under light microscopy to evaluate intracellular replication (mean number of parasites per cell in 100 infected cells) and infection index (percentage of infected cells per 100 examined cells). In contrast with HeLa cells, treatments with IL-10 or TGF-β1 induced a considerable augmentation in both T. gondii intracellular replication and invasion into BeWo cells. In addition, treatment with IFN-γ alone or associated with IL-10 or TGF-β1 increased the same parameters in BeWo cells, whereas the opposite effect was observed in HeLa cells. When endogenous IL-10 or TGF-β was blocked, both BeWo and HeLa cells were able to control the parasite infection only in the presence of IFN-γ. Together, these results indicate that the higher susceptibility of BeWo cells to T. gondii may be due to immunomodulation mechanisms, suggesting that the role of trophoblast cells in maintaining a placental microenvironment favourable to pregnancy may facilitate the infection into the placental tissues.
Determinants of natural immunity against tuberculosis in an endemic setting: factors operating at the level of macrophage–Mycobacterium tuberculosisinteraction
Authors: Gaikwad A N , Sinha Sudhir 
Published: July 2010

SummaryWe aimed to delineate factors operating at the interface of macrophage–mycobacterium interaction which could determine the fate of a ‘subclinical’ infection in healthy people of a tuberculosis-endemic region. Ten study subjects (blood donors) were classified as ‘high’ or ‘low’ responders based on the ability of their monocyte-derived macrophages to restrict or promote an infection with Mycobacterium tuberculosis. Bacterial multiplication between days 4 and 8 in high responder macrophages was significantly lower (P &lt; 0·02) than low responders. All donor sera were positive for antibodies against cell-membrane antigens of M. tuberculosis and bacilli opsonized with heat-inactivated sera were coated with IgG. In low responder macrophages, multiplication of opsonized bacilli was significantly less (P &lt; 0·04) than that of unopsonized bacilli. The levels of tumour necrosis factor (TNF)-α and interleukin (IL)-12 produced by infected high responder macrophages was significantly higher (P &lt; 0·05) than low responders. However, infection with opsonized bacilli enhanced the production of IL-12 in low responders to its level in high responders. The antibody level against membrane antigens was also significantly higher (P &lt; 0·05) in high responders, although the antigens recognized by two categories of sera were not remarkably different. Production of certain other cytokines (IL-1β, IL-4, IL-6 and IL-10) or reactive oxygen species (H2O2 and NO) by macrophages of high and low responders did not differ significantly. The study highlights the heterogeneity of Indian subjects with respect to their capability in handling subclinical infection with M. tuberculosis and the prominent role that TNF-α, opsonizing antibodies and, to a certain extent, IL-12 may play in containing it.
Intracellular adhesion molecule-1 up-regulation on thyrocytes by iodine of non-obese diabetic.H2h4 mice is reactive oxygen species-dependent
Authors: Sharma R , Traore K , Trush M A , Rose N R , Burek C Lynne 
Published: July 2010

SummaryIntracellular adhesion molecule-1 (ICAM-1) expression on the thyroid follicular cells of non-obese diabetic (NOD).H2h4 mice is enhanced by iodide treatment, which correlates with autoimmune thyroid disease in genetically susceptible NOD.H2h4 mice. The current study examines the mechanism of iodine-enhanced up-regulation of ICAM-1 on the surface of thyroid cells. We hypothesized that the up-regulation of ICAM-1 is due to a transient increase in production of reactive oxygen species (ROS). ROS may initiate signalling of the ICAM-1 gene promoter, enhancing up-regulated ICAM-1 protein on the cell surface. Single-cell suspensions of thyroid follicular cells from thyroiditis-susceptible NOD.H2h4 or non-susceptible BALB/c mice were treated in vitro with sodium iodide. Extracellular and intracellular ROS were assessed by luminol-derived chemiluminescence and flow cytometry assays respectively. Our results demonstrate that thyroid follicular cells of NOD.H2h4 generate higher levels of ROS compared with cells from non-susceptible strains of mice. Expression of a subunit protein of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p67phox, was analysed by Western blot immunoassay. A constitutive expression of the p67phox subunit protein was observed in NOD.H2h4 mice prior to iodine treatment. No such expression was found in BALB/c mice. Treatment of NOD.H2h4 thyroid cells with diphenyleneiodium, an inhibitor of NADPH oxidase, reduced generation of ROS and of ICAM-1 protein expression. Thus, thyrocytes from NOD.H2h4 mice produce enhanced levels of ROS that may be mediated by NADPH oxidase. Consequently, in NOD.H2h4 mice the ROS-induced signal for ICAM-1 up-regulation may contribute to mononuclear cellular infiltration of the thyroid gland and the progression of autoimmune thyroid disease.
Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats
Authors: Nielsen R H , Christiansen C , Stolina M , Karsdal M A 
Published: July 2010

SummaryAs anti-inflammatory treatments used in rheumatoid arthritis, such as glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen therapy (ET) on the development and activity of collagen-induced arthritis (CIA) in rats, with a focus on assessment of chondroprotective effects using biomarkers of type II collagen degradation. Forty female Lewis rats were allocated into four intervention groups: (i) control + vehicle; (ii) CIA + vehicle; (iii) CIA + ET; and (iv) CIA + prednisolone. During the 28-day intervention period we monitored body weight, time-point of disease onset, incidence of manifest disease and paw volume. Levels of the type II collagen degradation marker (CTX-II) were measured in serum. At euthanasia, hind paws were isolated, extracted for proteins and measured for the concentration of CTX-II. Matrix metalloproteinase (MMP) activity was evaluated using gelatinase zymography. Oestrogen treatment delayed the time-point of disease onset and reduced the incidence and degree of manifest immunoarthritis significantly, assessed by macroscopic evaluation of hind paw inflammation and paw volume. Measures of serum or tissue levels of CTX-II showed significantly reduced type II collagen degradation elicited by oestrogen treatment. In alignment, a decreased activity of MMP-2 and MMP-9 was found in the paw protein extracts. We have demonstrated that the anti-inflammatory effect of ET is linked to chondroprotective effects in an animal model of systemic immunoarthritis. As ET has positive rather than negative effects on bone health in contrast to prednisolone, these observations may be important for potential combination therapy.
Possible association between thyroid autoimmunity and Menière's disease
Authors: Fattori B , Nacci A , Dardano A , Dallan I , Grosso M , Traino C , Mancini V , Ursino F , Monzani F 
Published: July 2010

SummaryVarious aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear–vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66·7% TPO-Ab and 33·3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66·7% TPO-Ab and 33·3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0·0001 versus group A and group B) had significant autoantibody levels (68·4% TPO-Ab; 15·8% TPO-Ab + TR-Ab; 10·5% Tg-Ab; 5·2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.
Coeliac disease-specific autoantibodies targeted against transglutaminase 2 disturb angiogenesis
Authors: Myrsky E , Kaukinen K , Syrjänen M , Korponay-Szabó I R , Mäki M , Lindfors K 
Published: July 2010

Summary
Coeliac disease is characterized by immunoglobulin-A (IgA)-class autoantibodies targeted against transglutaminase 2 (TG2), a multi-functional protein also with a role in angiogenesis. These antibodies are present in patient serum but are also found bound to TG2 below the epithelial basement membrane and around capillaries in the small intestinal mucosa. Based on these facts and the information that the mucosal vasculature of coeliac patients on a gluten-containing diet is disorganized, we studied whether the coeliac disease-specific autoantibodies targeted against TG2 would disturb angiogenesis. The effects of coeliac disease-specific autoantibodies on in vitro angiogenesis were studied in angiogenic cell cultures. The binding of the antibodies to cells, endothelial sprouting, migration of both endothelial and vascular mesenchymal cells, the integrity of the actin cytoskeleton in both cell types and the differentiation of vascular mesenchymal cells were recorded. In vitro, IgA derived from coeliac disease patients on a gluten-containing diet binds to surface TG2 on endothelial and vascular mesenchymal cells and this binding can be inhibited by the removal of TG2. In addition, coeliac disease-specific autoantibodies targeting TG2 disturb several steps of angiogenesis: endothelial sprouting and the migration of both endothelial and vascular mesenchymal cells. Furthermore, the autoantibodies cause disorganization of the actin cytoskeleton in both capillary cell types that account most probably for the defective cellular migration. We conclude that coeliac disease-specific autoantibodies recognizing TG2 inhibit angiogenesis in vitro. This disturbance of the angiogenic process could lead in vivo to the disruption of the mucosal vasculature seen in coeliac disease patients on a gluten-containing diet.