Littérature scientifique sur le sujet « Immunomodulation of galf »

Diet is known to modulate immune functions in multiple ways and to affect host resistance to infections. Besides the essential nutrients, non-essential food constituents such as non-digestible carbohydrates may also have an impact on the immune system, especially in the area of the gut-associated lymphoid tissue (GALT). Recent data now provide first evidence that prebiotics such as inulin/oligofructose (IN/OF) modulate functions of the immune system. In animal studies IN/OF primarily activated immune cells in Peyer's patches including IL-10 production and natural killer (NK) cell cytotoxicity. Other immune functions modulated by IN/OF included the concentration of secretory IgA in ileum and caecum, splenic NK cell cytotoxicity as well as splenocyte cytokine production. In different tumour models, a lower incidence of tumours was observed, which in the case of colonic tumours was associated with enhanced NK cell cytotoxicity in the GALT. Few human studies so far have investigated the effects of IN/OF alone or in combination with other dietary supplements on immunocompetence. Supplementation of IN/OF resulted in minor changes of systemic immune functions such as decrease in phagocytic activity. No data are available on the effects of IN/OF on the GALT in man. The mechanisms of the reported effects of IN/OF on the immune system are currently investigated and include: (i) direct effects of lactic acid-producing bacteria or bacterial constituents on immune cells; (ii) the production of SCFA and binding to SCFA receptors on leucocytes. In conclusion, the current data suggest that IN/OF primarily modulate immune parameters in the GALT, but splenocytes are also activated by IN/OF. Human studies are needed to find out whether IN/OF have the potential to modulate systemic immunity in wellnourished individuals and to lower the risk of diseases such as colon cancer.

ABSTRACT We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-α production by inhibiting translation of the TNF-α mRNA. Elevated TNF-α levels in mice treated withd-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of γ-actins.

The gastrointestinal tract is a complex and dynamic ecosystem. Commensal microorganisms (C), which proliferate in the intestine from birth, are crucial for gut homeostasis while non commensal (NC) microorganisms are transient and enter the organism from the environment and foods. We studied comparatively the influence of oral administration of C and NC Lactobacillus fermentum and Lactobacilus acidophilus on the gut-associated lymphoid tissue (GALT) of conventional mice. To determine the importance of the selection of probiotic host-specificity bacteria with immunomodulating capacity, we examined the interaction with the gut by transmission electron microscopy and FITC-labelled bacteria. We compared the immunomodulation capacities of C and NC strains by studying the number of IgA secreting cells and cytokine profile. No differences were found in the number of IgA+ cells; however, the pattern of cytokine response to C and NC bacteria was different. With regard to proinflammatory cytokine (IFNγ and TNFα), we found that TNFα was mainly produced by NC bacteria, while C bacteria were able to elicit mainly IFNγ. The regulatory cytokines (IL-10 and IL-4) were induced with different patterns for both C and NC strains. No differences in the pathway of internalization to the gut between C and NC were found. In summary, we determined that C and NC bacteria interact with the intestine in the same way; both C and NC bacteria were able to reinforce the surveillance of the gut mucosal immune system. The cytokine profile showed that C bacteria would be involved in the regulation of intestinal homeostasis rather than in the immune activation as the NC bacteria.

In recent years, the structure of selenium-enriched polysaccharides and their application in immunomodulation have attracted much attention. In previous studies, we extracted and purified a novel selenium-enriched Pleurotus ostreatus polysaccharide called Se-POP-21, but its structure and immunomodulatory activity were still unclear. In this study, the main structural unit formula of Se-POP-21 was characterized by methylation analysis and an NMR experiment. The results showed that the backbone of Se-POP-21 was →[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]4→2,4)-β-L-Arap-(1→[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]4→, branched chain of β-D-Manp-(1→ and β-D-Manp-(1→4)-β-L-Arap-(1→ connected with →2,6)-α-D-Galp-(1→ and →2,4)-β-L-Arap-(1→,respectively, through the O-2 bond. In vitro cell experiments indicated that Se-POP-21 could significantly enhance the proliferation and phagocytosis of RAW264.7 cells, upregulate the expression of costimulatory molecules CD80/CD86, and promote RAW264.7 cells to secrete NO, ROS, TNF-α, IL-1β, and IL-6 by activating the NF-κB protein. The results of this study indicate that Se-POP-21 can effectively activate RAW264.7 cells. Thus, it has the potential to be used in immunomodulatory drugs or functional foods.

Probiotic agents have been shown to have significant clinical beneficial effects in the prevention and management of gastrointestinal and non-gastrointestinal conditions. These observations have led to work demonstrating that an important mechanism of these agents is their close interaction with the gut associated lymphoid tissue (GALT) and suggested immunomodulatory effects on systemic immune response. Studies on the possibility thatprebiotic agents might directly or indirectly induce similar immunomodulation have only recently begun. The preliminary findings of several recent human clinical trials reviewed in this article indicate that prebiotics may indeed prove to be a clinically beneficial dietary supplement, in the context of novel nutritional strategies for the management of gastrointestinal and systemic conditions.

The gastrointestinal tract is subjected to enormous and continual foreign antigenic stimuli from food and microbes. This organ must integrate complex interactions among diet, external pathogens, and local immunological and non-immunological processes. It is critical that protective immune responses are made to potential pathogens, while hypersensitivity reactions to dietary antigens are minimised. There is increasing evidence that fermentable dietary fibres and the newly described prebiotics can modulate various properties of the immune system, including those of the gut-associated lymphoid tissues (GALT). This paper reviews evidence for the immune-enhancing effects of dietary fibres. Changes in the intestinal microflora that occur with the consumption of prebiotic fibres may potentially mediate immune changes via: the direct contact of lactic acid bacteria or bacterial products (cell wall or cytoplasmic components) with immune cells in the intestine; the production of short-chain fatty acids from fibre fermentation; or by changes in mucin production. Although further work is needed to better define the changes, mechanisms for immunomodulation, and the ultimate impact on immune health, there is convincing preliminary data to suggest that the consumption of prebiotics can modulate immune parameters in GALT, secondary lymphoid tissues and peripheral circulation. Future protocols on the physiological impact of consuming prebiotics should be designed to include assessments of the gut microflora, gut physiology and the function and composition of the various regions of GALT.

The article presents data on classification, pathogenesis, clinical picture, diagnosis and differentiated treatment tactics, as well as practical algorithm for recognizing and preventing the development of drug-induced liver injury. Pathogenesis of drug-induced liver injury is analyzed, mechanisms of drug metabolism are explained, metabolism phases are described. Four main mechanisms of the pathological effect of drugs on the liver are identified: direct toxic effect on hepatocytes; toxic effect of drug metabolites; immunoallergic liver injury; idiosyncrasy. Peculiar attention is paid to the pathogenesis of drug-induced cholestasis. Direct hepatotoxic reactions develop according to the cytolytic (hepatocellular, parenchymal), cholestatic or mixed option. The most commonly diagnosed clinical variant of drug-induced liver injury is drug-induced hepatitis. Five forms of hepatitis induced by the use of pharmacological agents are distinguished: drug-induced hepatitis with an isolated increase in transaminases (anti-TB drugs, methyldopa, amiodarone, statins); acute hepatitis with jaundice; pseudo-surgical form of acute hepatitis: abdominal pain, fever, jaundice, enlarged gall bladder (cytostatics, antidepressants, antiarrhythmic drugs); severe forms of acute hepatitis with liver failure; chronic drug hepatitis. International diagnostic criteria, basic data on morphological liver changes are presented. Action of ursodeoxycholic acid is explained. It has a litholytic, anticholestatic, cytoprotective, immunomodulating, anti-inflammatory, antitoxic, hypocholesterolemic effect, modulates apoptosis, has a differentiated effect on the regeneration of hepatocytes.

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune-mediated. The aim of this study was to investigate the role of secondary lymphoid organs [mesenteric lymph nodes (MLN), gut-associated lymphoid tissue (GALT)] in IM-mediated FE by employing mice with deficient secondary lymphoid organs (aly/aly, MLN ex) or by administration of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720), an immunomodulating agent that inhibits emigration of lymphocytes out of lymphoid organs. Small bowel muscularis, and colonic muscularis from wild-type mice as control, from aly/aly mice, FTY720-treated mice (daily dose of 1.0 mg/kg mouse ip starting 3 days before surgical procedure), and wild-type mice that had undergone removal of mesenteric lymph nodes before IM (MLN ex mice) were obtained after selective IM of the jejunum or sham operation. FE was analyzed by measuring transit time of orally administered fluorescent dextran in the gastrointestinal tract [geometric center (GC) of fluorescent dextran], colonic transit time, infiltration of myeloperoxidase-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α] were determined by Taqman-PCR. We observed a significantly reduced upregulation of proinflammatory cytokines (IL-6, TNF-α, MIP-1α) in colonic muscularis of MLN ex mice, aly/aly mice, and FTY720-treated mice compared with wild-type mice. Contractility of circular muscularis strips of the colon but not the jejunum was significantly improved in aly/aly mice and FTY720-treated wild-type mice. Additionally, inflammation of the colon determined by the number of myeloperoxidase-positive cells and colonic transit time were significantly improved in aly/aly mice, FTY720-treated wild-type mice, and in MLN ex mice. In summary, lack of secondary lymphoid organs (MLN + GALT) in aly/aly mice or administration of FTY720 abrogated FE after IM as opposed to wild-type mice. These data demonstrate that secondary lymphoid organs are involved in the propagation of FE and postoperative ileus. FTY720 indirectly affects FE by inhibiting migration of activated T cells from the jejunum and adjacent secondary lymphoid organs to the colon. These findings support the crucial role of the adaptive immune system in FE, most likely by a sphyngosine 1-phosphate-dependent mechanism.

Lycopi Herba has been broadly used as a traditional medicinal herb in Asia due to its ability to strengthen immunity. However, it is still obscure for its material basis and underlying mechanisms. Polysaccharide, as one of the most important components of most natural herbs, usually contributes to the immunomodulatory ability of herbs. Here, we aimed to detect polysaccharides from Lycopi Herba and examine their potential immunomodulatory activity. A novel polysaccharide (LHPW) was extracted from Lycopi Herba and purified by DEAE-52 cellulose chromatography and G-100 sephadex. According to physicochemical methods and monosaccharide composition analysis, LHPW was mainly composed of galactose, glucose, fructose, and arabinose. NMR and methylation analyses indicated that LHPW was a neutral polysaccharide with a backbone containing →3,6)-β-D-Galp-(1→, →4)-β-D-Galp-(1→ and →4)-α-D-Glcp-(1→, with the branches of →1)-β-D-Fruf-(2→ and →6)-α-D-Galp-(1→. Immunological tests indicated that LHPW could activate macrophage RAW264.7 and promote splenocyte proliferation. This study discovered a novel polysaccharide from Lycopi Herba and showed it was a potential immunomodulator.

L’interleuchina-10 (IL-10) e’ una citochina immunosoppressiva con potenziale applicazione terapeutica in diverse malattie autoimmuni e infiammatorie. La somministrazione orale di questa citochina, da sola o in combinazione con autoantigeni associati alla malattia, potrebbe conferire protezione dall’insorgenza di specifiche malattie autoimmuni attraverso l’induzione di tolleranza orale. Un valido sistema alternativo per la produzione di proteine ricombinanti di interesse farmaceutico è rappresentato dalle piante transgeniche, data la possibilità di estendere la produzione su larga scala a bassi costi, e i minimi requisiti che richiedono per il loro mantenimento. Le piante, inoltre, possono essere assunte direttamente come alimento e potrebbero diventare esse stesse veicoli per la somministrazione delle proteine ricombinanti eliminando la necessità di purificarle. Ci si è proposti di valutare se le piante di tabacco fossero in grado di produrre alti livelli di IL-10 virale e murina biologicamente attiva. Per ottenere alti livelli di espressione dei transgeni, sono state effettuate sia la trasformazione dei plastidi, sia la trasformazione nucleare, valutando diverse strategie di localizzazione delle proteine ricombinanti. La trasformazione dei cloroplasti è risultato un approccio non attuabile per la produzione di IL-10 virale o murina ricombinante, in quanto i livelli di accumulo sono risultati decisamente insoddisfacenti per entrambi i transgeni. Invece, per quanto riguarda la trasformazione nucleare, sono state valutate tre diverse strategie di localizzazione sub-cellulare, per dirigere la proteina ricombinante nel reticolo endoplasmico (RE), nel citosol e nell’apoplasto, dapprima in esperimenti di espressione transiente e, successivamente, sono state generate piante transgeniche stabili con il costrutto che aveva fornito i più alti livelli di accumulo indirizzando la proteina nel RE. Le proteine ricombinanti sono state purificate da materiale fogliare transgenico e sono state caratterizzate rispetto alla composizione degli N-glicani, alla dimerizzazione, alla loro stabilità e attività biologica in saggi in vitro. Entrambe le molecole prodotte in pianta formano dimeri stabili, e sono in grado di attivare la cascata di trasduzione del segnale di IL-10 e di indurre risposte anti-infiammatorie specifiche nella linea cellulare di macrofagi murini J774. E’ stato dimostrato che le piante di tabacco sono in grado di processare correttamente l’IL-10 virale e murina in dimeri biologicamente attivi, e che quindi rappresentano una valida piattaforma per la produzione di queste citochine. Inoltre, i livelli di accumulo ottenuti sono sufficientemente elevati da permettere di somministrare una dose immunologicamente rilevante di IL-10 in una ragionevole quantità di materiale fogliare, senza richiedere laboriose purificazioni. Questo lavoro apre la strada alla realizzazione di studi di somministrazione orale in modelli murini di malattie autoimmuni, che permetteranno di effettuare una valutazione comparativa delle proprietà immunomodulatorie nonché dell’efficacia delle IL-10 virale e murina nell’indurre tolleranza orale.
Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, with therapeutic applications in several autoimmune and inflammatory diseases. Oral administration of this cytokine, alone or in combination with disease-associated autoantigens, could confer protection form the onset of a specific autoimmune disease through the induction of oral tolerance. Transgenic plants are attractive systems for production of therapeutic proteins because of the ability to do large scale-up at low cost, and the low maintenance requirements. They are highly amenable to oral administration and could become effective delivery systems without extensive protein purification. The ability of tobacco plants to produce high levels of biologically-active viral and murine IL-10 was investigated. To reach high accumulation levels of the transgenes, plastid transformation of the IL-10 genes as well as different targeting strategies of the nuclear encoded recombinant proteins were investigated. Chloroplast transformation turned out not to be a feasible approach for the recombinant production of IL-10, as unsatisfactory accumulation levels were obtained upon expression of both transgenes. For tobacco nuclear transformation, three different subcellular targeting strategies, directing the recombinant protein into the endoplasmic reticulum (ER), cytosol and apoplast, were first assessed in transient expression experiments, and stable transgenic plants were then generated with the constructs that yielded the highest accumulation levels by targeting the recombinant proteins to the ER. The recombinant proteins were purified from transgenic leaf material and characterized in terms of their N-glycan composition, dimerization, stability and biological activity in in vitro assays. Both molecules formed stable dimers, were able to activate the IL-10 signaling pathway and to induce specific anti-inflammatory responses in mouse J774 macrophage cells. It was therefore demonstrated that tobacco plants are able to correctly process viral and murine IL- 10 into biologically active dimers, representing a suitable platform for the production for these cytokines. The accumulation levels obtained are high enough to allow delivery of an immunologically relevant dose of IL-10 in a reasonable amount of leaf material, without extensive purification. This study paves the way to performing feeding studies in mouse models of autoimmune diseases, that will allow evaluation of the immunomodulatory properties and effectiveness of the viral and murine IL-10 in inducing oral tolerance.