Immunogenicity Evaluation of a DNA Vaccine Expressing the Hepatitis C Virus Non-Structural Protein 2 Gene in C57BL/6 Mice

Backgrounds: Most of the hepatitis C virus (HCV) infections elicit poor immune responses and 75% to 85% of cases become chronic; therefore, the development of an effective vaccine against HCV is of paramount importance. In this study, we aimed to evaluate co-administration of HCV non-Structural Protein 2 and IL-12 DNA vaccines in C57BL/6 mice. Methods: A plasmid encoding full-length HCV NS2 protein (non-structural protein 2) was generated and used to vaccinate mice. Negative control (an empty expression vector) was also employed to evaluate the background response. To investigate immune responses against vaccine, C57BL/6 mice received three doses of the vaccine with a two-week interval. Cellular immunity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay for lymphocyte proliferation, lactate dehydrogenase release for cytotoxic T lymphocyte (CTL) activity and cytokine assay. Results: The findings demonstrated that immunization of mice with plasmid expressing HCV NS2 induced CTL response, interferon gamma production, and lymphocyte proliferation compared to negative control. The results also demonstrated that co-administration of IL-12 with the HCV NS2 plasmid induced significantly better immune response in C57BL/6 mice. Conclusion: DNA vaccine encoding HCV NS2 is an effective candidate that can trigger CTL-based immune response against HCV. In addition, the results suggested that combining the DNA vaccine approach with immune stimulatory cytokines may significantly enhance antigen-specific immune responses. Key Words: Hepatitis C virus (HCV), NS2 protein, DNA vaccine, IL-12     

Effect of Schlafen 2 on natural killer and T cell development from common T/natural killer progenitors

Natural Killer (NK) cells are thought to develop from common lymphoid progenitors in the bone marrow. Even though thymus is not essential for NK cell development, T-cell/natural killer-cell (T/NK) precursors, DN1 (CD44+CD25-) and DN2 (CD44+CD25+) when cultured on an OP9 stroma, give rise to some NK1.1 cells. Genes of the Schlafen (Slfn) family are involved in hematopoietic and immune processes. The contribution of the Slfn genes in NK cell development from Double Negative (DN) cells is unknown. We transduced DN1 and DN2 progenitors prepared from C57BL/6 (B6) mouse thymus with Schlafen 1 (Slfnl) and Schlafen 2 (Slfn2) genes using Mig retroviral vector containing the Green Fluorescent Protein (GFP) gene and cultured those transduced progenitors on OP9 and OP9 stroma expressing the Notch ligand Delta-like 1 (OP9-DL 1) with appropriate cytokines to see if they affect generating NK and T-cells differently. Maturation of both NK and T cells from immature T/NK thymocytes hampered by Slfn1 and Slfn2 transduction but we got a small number of Slfn1 and Slfn2 expressing cells upon culture of transduced DN progenitors on stroma cells. There was no difference between Slfn1 expressing (GFP+) and none expressing T cells regarding CD3 expression but all mature NK cells were from Slfn1 negative population. Slfn2 completely blocked maturation of T cells but there was no difference between Slfn2 expressing and none expressing NK cells. Based on our findings both Slfn1 and Slfn2 interfere with maturation of DN2 progenitors but T cell development is more sensitive to Slfn2 expression than NK cell.     

Comparative Analysis of CD4+ and CD8+ T Cells in Tumor Tissues,Lymph Nodes and the Peripheral Blood from Patients with Breast Cancer

Background: CD4+ and CD8+ T cells are the main types of lymphocytes in cell-mediated immunity and play a central role in the induction of efficient immune responses against tumors. The frequencies of T cell subtypes in the peripheral blood and tumor tissues, and draining lymph nodes (dLN) can be considered as useful markers for evaluation of the immune system in cancers. Methods: In this study, the frequencies of CD4+ and CD8+ T cells in blood, tumor tissues, and dLN samples of breast cancer patients were compared with each other and with similar tissues from normal individuals. Immunophenotyping was carried out by flow cytometry and the expression levels of CXCL10, granzyme B, and mammaglobin were evaluated by real-time PCR. Results: In the peripheral blood, there were no differences in the T cell subsets between the patients and the normal individuals. The frequency of CD8+ T cells was significantly higher in tumor tissue than normal breast tissues while granzyme B expression was similar. Based on mammaglobin expression levels, dLN have been classified into micro- and macro-metastatic dLN. We found significantly lower frequency of CD4+ in macro-metastatic dLN than micro-metastatic dLN. CD8+ frequency was similar in both dLN; however, granzyme B expression was higher in micro-metastatic ones. There was not any significant difference in CXCL10 expression between the two types of dLN. Conclusion: Based on our results, although the tumor does not affect the systemic immunity, tumoral cells affect the local immune system in the tumoral tissues and the metastatic dLN. Key Words: Breast neoplasms, CD4+ T lymphocyte, CD8+ T lymphocytes, CXCL10, Granzymes     

Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases

Background

Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature.

Presentation of the hypothesis

Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies.

Testing the hypothesis

Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes of human disease-associated HLA determinants and T or B cell receptors, as well as in vitro binding studies employing purified HLA proteins, synthetic peptides, and cellular assays with antigen-presenting cells and patient's lymphocytes. Indisputably, a bioinformatics-based search for peptide motifs and the modeling of the conformation of bound autoantigenic peptides associated with their respective HLA alleles will reveal some of these important processes.

Implications of the hypothesis

The elucidation of HLA-restricted immune recognition mechanisms prompting the production of two or more disease-specific autoantibodies holds significant clinical ramifications and implications for the development of more effective treatment protocols.

     

Two New Lyngbyatoxin Derivatives from the Cyanobacterium,Moorea producens

The toxin-producing cyanobacterium, Moorea producens, is a known causative organism of food poisoning and seaweed dermatitis (also known as “swimmer’s itch”). Two new toxic compounds were isolated and structurally elucidated from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies, as well as optical rotations and CD spectra indicated two new lyngbyatoxin derivatives, 2-oxo-3(R)-hydroxy-lyngbyatoxin A (1) and 2-oxo-3(R)-hydroxy-13-N-desmethyl-lyngbyatoxin A (2). The cytotoxicity and lethal activities of 1 and 2 were approximately 10- to 150-times less potent than lyngbyatoxin A. Additionally, the binding activities of 1 and 2 possessed 10,000-times lower affinity for the protein kinase Cδ (PKCδ)-C1B peptide when compared to lyngbyatoxin A. These findings suggest that these new lyngbyatoxin derivatives may mediate their acute toxicities through a non-PKC activation pathway.     

A ω-secalin contained decamer shows a celiac disease prevention activity

Celiac disease (CD) is an autoimmune permanent enteropathy that is triggered in susceptible individuals after the ingestion of gluten, a storage protein fraction presents in wheat, rye and barley endosperm. Specific gluten peptides can bind to HLA-DQ2/8 and induce lamina propria CD4⁺ T cell responses causing damage of the small intestine mucosa. Recent studies suggested that beside immunodominant and toxic epitopes, wheat gluten also contains epitopes capable of preventing the mucosal response in vitro. Among them, a decapeptide (QQPQDAVQPF) from wheat was reported to have an antagonist effect on the agglutination of K562(S) cells and celiac T-cell activation, although the corresponding nucleotidic sequence remained unknown. This study was therefore designed to clone the sequence encoding the protein carrying the decapetide with CD protective properties. A ω-secalin gene encoding containing the decapeptide QQPQRPQQPF was isolated. Although the decapeptide was not identical to the one previously described, QQPQRPQQPF showed the same capability to prevent K562(S) cell agglutination and celiac mucosa immune activation induced by toxic gliadins. The ω-secalin gene was found in wheat carrying the wheat–rye chromosomal translocations 1BL.1RS. The identification of this immunomodulatory gliadin sequence, naturally occurring in cultivars of wheat toxic for celiac patients, might offer new therapeutic strategies for CD.     

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”.     

Endothelial cell activation and neovascularization are prominent in dermatomyositis

Background

While vascular and immune abnormalities are common in juvenile and adult dermatomyositis (DM), the molecular changes that contribute to these abnormalities are not clear. Therefore, we investigated pathways that facilitate new blood vessel formation and dendritic cell migration in dermatomyositis.

Methods

Muscle biopsies from subjects with DM (9 children and 6 adults) and non-myositis controls (6 children and 7 adults) were investigated by immunohistochemistry using antibodies that recognize existing (anti-CD146) and newly formed blood vessels (anti-αVβ3) and mature dendritic cells (anti-DC-LAMP). Blood vessel quantification was performed by digitalized image analysis. Additional muscle biopsies from subjects with adult DM and non-myositis controls were used for global gene expression profiling experiments.

Results

A significant increase in neovascularization was found in muscle biopsies of DM patients; neovascularization (αVβ3 positive capillaries and vessels per muscle fiber) was much higher in juvenile than in adult DM patients (control vs juvenile DM: Mean ± SE: 0.06 ± 0.01 vs 0.6 ± 0.05; p < 0.0001 and control vs adult DM: Mean ± SE: 0.60 ± 0.1 vs 0.75 ± 0.1; p = 0.051). Gene expression analysis demonstrated that genes that participate not only in angiogenesis but also in leukocyte trafficking and the complement cascade were highly up regulated in DM muscle in comparison to age matched controls. DC-LAMP positive dendritic cells were highly enriched at perivascular inflammatory sites in juvenile and adult DM patients along with molecules that facilitate dendritic cell transmigration and reverse transmigration (CD142 and CD31).

Conclusion

These results suggest active neovascularization and endothelial cell activation in both juvenile and adult DM. It is likely that close association of monocytes with endothelial cells initiate rapid dendritic cell maturation and an autoimmune response in DM.

     

Gluten and non-gluten proteins of wheat as target antigens in autism,Crohn’s and celiac disease

Studies show that patients with celiac disease react not only with gluten wheat proteins but also with non-gluten wheat components. Our goal was to measure IgG or IgA antibodies against wheat proteins or peptides that would provide the most sensitive method for the detection of wheat immune reaction in children with autism spectrum disorder, and patients with Crohn’s and celiac disease (CD). Using ELISA, we measured these antibodies against various gluten and non-gluten wheat proteins. Compared to controls in all three conditions, the strongest reaction was against CXCR3-binding gliadin peptide, followed by a wheat protein mixture, and α-gliadin 33-mer peptide. We determined that a sample that strongly reacted against non-gluten proteins also reacted strongly against gluten proteins. We also found that IgA antibodies against CXCR3-binding gliadin peptide were strongly reactive in a subgroup of 33% in the autism group, 42% in the Crohn’s group, and all tested samples with CD. The results indicate that measuring IgG and IgA antibodies against non-gluten proteins adds nothing to the pathologic relevance of these antibodies. Further research is needed on CXCR3-binding gliadin peptide antibodies as a possible biomarker and as a guide for dietary elimination in CD, Crohn’s disease and a subgroup of children with ASD.     

Interferon-gamma low producer genotype +5644 over presented in patients with focal brucellosis

Genetic polymorphisms that affect production levels of certain cytokines may determine the risk, severity or protection in some infectious diseases like brucellosis. IFN-gamma plays a key role in the defense mechanism against brucella infection. This study aimed to determine the influence of the polymorphism within the +5644 position of IFN-gamma gene on the susceptibility to brucellosis. We investigated the allelic and genotypes distribution of A5644G polymorphism in IFN-gamma gene in an Iranian population comprising 259 patients with brucellosis and 238 healthy controls. The single nucleotide polymorphism was determined using the polymerase chain reaction in association with sequence-specific primers (PCR-SSP) incorporating mismatches at the 3'-end. Allelic and genotype frequencies of G5644A polymorphism of IFN-gamma gene were not significantly differed between patients with brucellosis and controls (p > 0.05). Stratification of patients to focal and non focal diseases revealed a significant increased of 5644A allele in patients with focal brucellosis (79.31% vs. 61.94%, p = 0.0005). Moreover, multivariate logistic regression models showed patients harboring the INF-y G5644A genotype were significantly more likely to develop focal infectious complications (OR = 3.45, p = 0.0004, 95% CI = 1.26-7.94). The present study suggests that the variant genotypes of G6544A of IFN-gamma might be associated with focal form of brucellosis and play as a genetic risk factor in brucellosis.     

大豆过敏原Gly m 4蛋白抗原表位特征预测

通过生物信息学相关软件分析大豆过敏原Gly m 4蛋白理化性质(Prot Param)、信号肽(Signal P 4.1 Server)、跨膜区(TMHMM Server V 2.0)、B细胞表位(DNAStar)、MHC-Ⅱ类分子的结合能力(Net MHCⅡ2.2)。结果发现:Gly m4蛋白稳定性较好,无信号肽与跨膜区,转角结构丰富;B细胞抗原表位预测表明,Gly m 4蛋白61~64、93~94、122~125、127~130、134~137区域是潜在B细胞抗原表位;MHC-Ⅱ类分子的结合力分析表明Gly m 4蛋白144~153区域及82~96区域是潜在T细胞抗原表位,同时发现HLA-DRB10701、HLA-DRB10101等位基因型人群对Gly m 4蛋白较敏感。Gly m 4蛋白抗原表位分析为大豆过敏原的低过敏原性改造提供参考依据。     

Woodchuck Hepatitis Virus Post-Transcriptional Regulation Element (WPRE) Promotes Anti-CD19 BiTE Expression in Expi293 Cells

Background:Bispecific antibodies represent an important class of mAbs, with great therapeutic potentials due to their ability to target simultaneously two distinct epitopes. The generation of functional bispecific antibodies with the highest possible yields is particularly critical for the production of these compounds on industrial scales. Anti- CD3 × CD19 bsAb is a bispecific T-cell engager (BiTE) currently used for treating ALL. Herein, we have tried to optimize the expression level of this antibody in mammalian hosts. Methods:WPRE sequence was incorporated at the 3’ end of the expression cassette. This modification resulted in a notable about two-fold increase in the expression of the bsAb in the Expi293 cell line. Results & Conclusion:Follow-up flow cytometry analysis demonstrated the binding properties of the produced antibody at acceptable levels, and in vitro bioactivity assays showed that this product is potent enough for targeting and destroying CD19-positive cells. Our findings show that WPRE enhances the expression of this type of bispecific mAbs in HEK-293 family cell lines. This approach can be used in biopharma industry for the mass production of anti-CD3 × CD19 bispecific antibody. Key Words: Acute lymphoblastic leukemia, Bispecific antibodies, Monoclonal antibody     

A New Lyngbyatoxin from the Hawaiian Cyanobacterium Moorea producens

Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of “swimmer’s itch” with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies revealed the isolated compound had the same planar structure with that of lyngbyatoxin A. The results of optical rotation and CD spectra indicated that the compound was a new lyngbyatoxin A derivative, 12-epi-lyngbyatoxin A (1). While 12-epi-lyngbyatoxin A showed comparable toxicities with lyngbyatoxin A in cytotoxicity and crustacean lethality tests, it showed more than 100 times lower affinity for protein kinase Cδ (PKCδ) using the PKCδ-C1B peptide when compared to lyngbyatoxin A.     

Human leukocyte antigen-G expression on dendritic cells induced by transforming growth factor-beta1 and CD4+ T cells proliferation

Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-Beta1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is to evaluate the effect of TGF-Beta1 on the induction of human leukocyte antigen-G (HLA-G) expression on the DC which is derived from monocyte. Methods: In this study, we evaluated the effect of TGF-Beta1 in induction HLA-G expression on the monocyte-derived DC by flowcytometry and then CD4+ T cell proliferative responses in the presence of DC-treated TGF-Beta1 was studied. Results: The results of this study showed that DC bearing HLA-G down-regulated activation of CD4+ T cells and production of IL-6 and IL-17 in comparison with control (P<0.05). Conclusion: It is concluded that TGF-Beta1 has an important regulatory role in CD4+ T cell proliferation by increasing HLA-G on DC and these cells can probably prevent unexpected immune responses in vivo.     

Potato yield losses due to early blight in Minnesota fields, 1981 and 1982

In both 1981 and 1982, 51 potato fields were surveyed every 7–10 days for early blight severity and fungicide use. Early blight severity data from each field were used as input to a regression model to estimate yield loss in that field. The model for early maturing potato cultivars was Percent Yield Loss=0.8183+0.6441* (% blight increment between days 56 and 66)+0.6102* (% blight increment between days 66 and 76)+1.3480* (% blight increment between days 76 and 86). The model for late maturing cultivars was Percent Yield Loss=2.1846-4.7734* (% blight on day 56)+0.7440* (% blight on day 76)+ 0.5676* (% blight on day 96). In both 1981 and 1982, early blight was found to be present in all fields of the survey. In 1981, early blight was estimated to have caused mean losses of 6.5% (Red River Valley), 3.7% (Central sands) and 2.3% (Southern muck). In 1982, losses from the same areas were 5.4%, 3.7% and 2.6% respectively. In 1981, individual county losses ranged from 2.3% for Freeborn to 12.9% for Marshall while in 1982 losses were from 2.0% for Freeborn to 6.7% for Clay. Although fungicide use data were incomplete, the county with lowest yield loss had the most fungicide applications.     

Expression of the Antimicrobial Peptide Piscidin 1 and Neuropeptides in Fish Gill and Skin: A Potential Participation in Neuro-Immune Interaction

Antimicrobial peptides (AMPs) are found widespread in nature and possess antimicrobial and immunomodulatory activities. Due to their multifunctional properties, these peptides are a focus of growing body of interest and have been characterized in several fish species. Due to their similarities in amino-acid composition and amphipathic design, it has been suggested that neuropeptides may be directly involved in the innate immune response against pathogen intruders. In this review, we report the molecular characterization of the fish-specific AMP piscidin1, the production of an antibody raised against this peptide and the immunohistochemical identification of this peptide and enkephalins in the neuroepithelial cells (NECs) in the gill of several teleost fish species living in different habitats. In spite of the abundant literature on Piscidin1, the biological role of this peptide in fish visceral organs remains poorly explored, as well as the role of the neuropeptides in neuroimmune interaction in fish. The NECs, by their role as sensors of hypoxia changes in the external environments, in combination with their endocrine nature and secretion of immunomodulatory substances would influence various types of immune cells that contain piscidin, such as mast cells and eosinophils, both showing interaction with the nervous system. The discovery of piscidins in the gill and skin, their diversity and their role in the regulation of immune response will lead to better selection of these immunomodulatory molecules as drug targets to retain antimicrobial barrier function and for aquaculture therapy in the future.     

Hormaomycins B and C: New Antibiotic Cyclic Depsipeptides from a Marine Mudflat-Derived Streptomyces sp.

Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2-nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and β-methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria.     

Corrective role of chickpea intake on a dietary-induced model of hypercholesterolemia

A feeding trial was conducted in order to evaluate the potential effect on the lipid profile in a experimentally induced situation of hypercholesterolemia of a previously uninvestigated legume (Cicer aretinum L.) widely included in Mediterranean and Latinamerican human diets. Rats fed on a hypercholesterolemic diet containing saturated fat, cholesterol and cholic acid (H) had 123 percent higher serum cholesterol and 62 percent greater triacylglycerols levels than the animals receiving casein (C) protein. The LDL and VLDL cholesterol levels were 1330 percent and 35 percent higher, respectively, and HDL cholesterol 34 percent lower in the group of animals given the H diet as compared to controls. Further feeding of the hypercholesterolemic rats with animal protein (HC) resulted in a significant decrease of triacylglycerols (–70 percent), which reflected the decrease in the VLDL fraction. These effects on the lipid metabolism were more marked when the legumeCicer aretinum L. was present in the diet (HL). Significantly decreased concentrations of total cholesterol (–54 percent) and triacylglycerols (–70 percent) as well as the levels of LDL (–54 percent) and VLDL (–70 percent) were seen in rats fed chickpeas. In conclusion, a differential hypocholesterolemic effect between dietary casein and chickpea intake in a model of hypercholesterolemia induced by the diet was found, with beneficial effects on the lipid metabolism when legume was included in the diet as compared to casein. This suggests, for apparently the first time, that chickpea consumption may have a corrective effect in some alterations of the lipid profile.Abbreviations ANF Antinutritional factors - CD Cardiovascular disease - C Casein diet (Control diet) - H Hypercholesterolemic diet - L Legume diet - SD standard deviation     

Astaxanthin Protects Dendritic Cells from Lipopolysaccharide-Induced Immune Dysfunction

Astaxanthin, originating from seafood, is a naturally occurring red carotenoid pigment. Previous studies have focused on its antioxidant properties; however, whether astaxanthin possesses a desired anti-inflammatory characteristic to regulate the dendritic cells (DCs) for sepsis therapy remains unknown. Here, we explored the effects of astaxanthin on the immune functions of murine DCs. Our results showed that astaxanthin reduced the expressions of LPS-induced inflammatory cytokines (TNF-α, IL-6, and IL-10) and phenotypic markers (MHCII, CD40, CD80, and CD86) by DCs. Moreover, astaxanthin promoted the endocytosis levels in LPS-treated DCs, and hindered the LPS-induced migration of DCs via downregulating CCR7 expression, and then abrogated allogeneic T cell proliferation. Furthermore, we found that astaxanthin inhibited the immune dysfunction of DCs induced by LPS via the activation of the HO-1/Nrf2 axis. Finally, astaxanthin with oral administration remarkably enhanced the survival rate of LPS-challenged mice. These data showed a new approach of astaxanthin for potential sepsis treatment through avoiding the immune dysfunction of DCs.