Animals ; Anti-Bacterial Agents ; administration & dosage ; Escherichia coli ; Female ; Galactosylceramides ; immunology ; Gastric Mucosa ; pathology ; Gastritis, Atrophic ; pathology ; Helicobacter Infections ; complications ; drug therapy ; Helicobacter pylori ; pathogenicity ; Humans ; Inflammation ; pathology ; Intestines ; microbiology ; Levofloxacin ; Lymphocyte Activation ; Male ; Natural Killer T-Cells ; microbiology ; Ofloxacin ; administration & dosage ; Sphingomonas ; Stomach ; pathology

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although alpha-galactosylceramide (alpha-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-gamma by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.
Antigen-Presenting Cells ; B-Lymphocytes* ; Coculture Techniques ; Dendritic Cells ; Galactosylceramides ; Interleukin-4 ; Natural Killer T-Cells*

OBJECTIVETo investigate the effect of sea cucumber cerebroside(SCC) and its long-chain base(LCB) on lipid and glucose metabolism in obese mice.

METHODSThe mouse obese model was established by feeding high fat diet. The mice were randomly assigned to 4 groups: control group, model group, SCC group and LCB group. After 4 weeks, the glucose tolerance test was undertaken. After 5 weeks, the body fat content, organic indexes, serum lipid level, glycemic index and liver lipid level were determined.

RESULTSCompared with the model group, the glucose tolerance in the SCC group and LCB group was ameliorated significantly (P<0.01, P<0.05); glycemic index (P<0.01, P<0.01), the weight of adipose tissue (P<0.05, P<0.01) and the hepatic TG were reduced significantly (P<0.05, P<0.05).

CONCLUSIONSea cucumber cerebroside and its long-chain base can improve the glucose and lipid metabolism in obese mice.

Animals ; Blood Glucose ; metabolism ; Cerebrosides ; pharmacology ; Lipid Metabolism ; Lipids ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity ; blood ; drug therapy ; Sea Cucumbers ; chemistry

PURPOSE: Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma. METHODS: Because increased alpha-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, alpha-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naive BALB/c mice. Intracellular IL-4 and IFN-gamma were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined. RESULTS: Intranasal administration of LPS, flagellin, or CpG reduced development of alpha-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-gamma from alpha-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb. CONCLUSIONS: TLR4, 5, and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists.
Administration, Intranasal ; Animals ; Asthma ; Bronchoalveolar Lavage ; Cytokines ; Eosinophils ; Flagellin ; Galactosylceramides ; Humans ; Inflammation ; Interleukin-12 ; Interleukin-4 ; Mice ; Natural Killer T-Cells ; Spleen

OBJECTIVETo explore the effect of α- galactosyleramide( α-GalCer ) on immune reconstitution under acute graft-versus-host disease (aGVHD).

METHODSBALB/c mice were transplanted wit hallogeneic C57BL/6 bone marrow cells and splenocytes (both 1×10(7))after receiving lethal total-body irradiation. α-GalCer (100 ug/kg) or vehicle (dimethylsulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitution,proliferation of T cells and B cells, hematopoiesis,and thymic microenvironment were assessed.

RESULTSThe α-GalCer group exhibited higher percentages of CD3(+),CD4(+), CD8(+), B220(+), CD40(+), and CD86(+)cells compared with the vehicle group . The number of colony forming unit per 1000 CD34(+) cells in the α-GalCer group was higher than in the vehicle group ( P=0.0012).In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3(+), CD4(+), CD8(+),and B220(+) cells compared with the vehicle group. As for the results of in vivo proliferation assays, the numbers of CD3(+), CD4(+), CD8(+), and B220(+)cells were higher in the α-GalCer group than in the normal group ,especially the number of B220(+) cells ( P=0.007).Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3(+), CD4(+), and CD8(+) cells.

CONCLUSIONAdministration of α-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.

Animals ; B-Lymphocytes ; drug effects ; immunology ; Bone Marrow Transplantation ; immunology ; Female ; Galactosylceramides ; pharmacology ; Graft vs Host Disease ; immunology ; Hematopoietic Stem Cells ; drug effects ; Lymphocyte Activation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes ; drug effects ; immunology ; Transplantation, Homologous

BACKGROUNDActivation in vitro of natural killer T (NKT) cells in systemic lupus erythematosus (SLE) with α-galactosylceramide (α-GalCer) and dendritic cells (DC) may affect the immunoregulatory role of NKT cells. This study was designed to compare the number of NKT cells in patients with SLE to the number in healthy volunteers and measure the cytokines secreted from these NKT cells in vitro.

METHODSThree sets of culture conditions using (i) α-GalCer, (ii) DC, or (iii) both α-GalCer and DC (α-GalCer+DC) were adopted to expand NKT cells from peripheral blood mononuclear cells (PBMC) of patients with SLE and healthy volunteers. Flow cytometry was used to assess the levels of interleukin (IL)-4, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by the Vα24(+)Vβ11(+) NKT cells.

RESULTSAfter 14 days in culture, the total cell count and percentage of Vα24(+)Vβ11(+) NKT cells were increased under all conditions but were highest in the α-GalCer+DC group. The level of IL-4 and IL-10 secreted by Vα24(+)Vβ11(+) NKT cells from patients with active SLE was found to be higher than that of inactive patients and the control group (P < 0.05), while the levels of IFN-γ and TNF-α were lower than those found in the inactive and control groups (P < 0.05).

CONCLUSIONSVα24(+)Vβ11(+) NKT cells showed the greatest expansion in vitro with α-GalCer and DC. Th2-type cytokines from Vα24(+)Vβ11(+) NKT cells are the predominant type in patients with SLE, while Th1 cytokines predominate in the control group. This evolution of NKT cell function during the progression of the disease may have important implications in understanding the mechanism of SLE and for the development of possible therapies using NKT cell agonists.

Adolescent ; Adult ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cytokines ; metabolism ; Dendritic Cells ; metabolism ; Female ; Flow Cytometry ; Galactosylceramides ; pharmacology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-4 ; metabolism ; Lupus Erythematosus, Systemic ; immunology ; metabolism ; Male ; Middle Aged ; Natural Killer T-Cells ; cytology ; drug effects ; metabolism ; Receptors, Antigen, T-Cell ; metabolism ; Receptors, Antigen, T-Cell, alpha-beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Young Adult

Animals ; Female ; Galactosylceramides ; metabolism ; Graft vs Host Disease ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes ; cytology ; Th2 Cells ; cytology

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called Valpha14Jalpha18 in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, alpha-galactosylceremide (alpha-GalCer), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and interferon-gamma. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with alpha-GalCer. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.
Animals ; Antigen-Presenting Cells ; Asthma ; Autoimmune Diseases ; Colitis ; Communicable Diseases ; Encephalomyelitis, Autoimmune, Experimental ; Galactosylceramides ; Humans ; Interferon-gamma ; Interleukin-4 ; Mice ; Natural Killer T-Cells ; Receptors, Antigen, T-Cell ; T-Lymphocytes ; Thyroid Gland ; Thyroiditis ; Viruses

OBJECTIVETo investigate the effect of sea cucumber cerebroside (SCC) on the lipid metabolism in rats with orotic acid-induced fatty liver.

METHODSThe non-alcoholic fatty liver disease (NAFLD) model was established by adding orotic acid to the diets in rats. The rats were randomly assigned to four groups:control group, NAFLD group, NAFLD + low SCC group and NAFLD + high SCC group. After 10 days of feeding, the serum and hepatic lipid concentrations and the aminopherase activities were measured; the composition of hepatic fatty acids was also analyzed.

RESULTThe serum TC and TG levels reduced significantly in the NAFLD group as compared with the controls (P<0.05), while the sea cucumber cereborside feeding raised the serum lipid concentrations (P<0.05). The hepatic TC and TG levels dramatically increased in the NAFLD group in comparison with the controls (P<0.05, P<0.01), while the hepatic lipid accumulations decreased in both SCC groups (P<0.05, P<0.01). The ALT and AST activities in the NAFLD group increased markedly when compared with the controls (P<0.05, P <0.01), while the sea cucumber cerebroside feeding attenuated the hepatic injury levels (P<0.05, P<0.01). Compared with the control group, the stearoyl-CoA desaturase (SCD) activity increased significantly in the NAFLD group (P<0.05), but decreased in SCC groups (P<0.05).

CONCLUSIONSea cucumber cerebroside can attenuate the rat fatty liver induced by orotic acid.

Animals ; Cerebrosides ; administration & dosage ; pharmacology ; Disease Models, Animal ; Fatty Acids ; metabolism ; Fatty Liver ; drug therapy ; metabolism ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sea Cucumbers ; chemistry

Immune reconstitution is crucially relevant for patients receiving hematopoietic stem cell transplantation (HSCT). This study was purposed to investigate the ability of α-GalCer (α-galactosylceramide), a well-known activator of natural killer T cells (NK-T), to enhance immune and hematological reconstitution. Lethally irradiated BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes. α-GalCer was administered immediately after HSCT. After transplantation, the weight, activity, hairs, diarrhea and survival time of mice were observed daily; the blood routine test was performed once weekly; the donor chimeras, amount of mononuclear cells in spleen (MNC) and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD11c(+), CD40(+), CD86(+) and CD80(+) cells were detected by FACS on day 2, 7, 14, 27, 70 after transplantation. The results indicated that the MNC counts and relative levels of CD3(+) and CD4(+) in group treated with α-GalCer on day 2 after transplantation were higher than those in control group; at the same time, the detected donor chimeras were complete recipient type chimeras, then gradually transformed into donor type, on day 7 - 14 donor chimeras in α-GalCer group were enhanced significantly as compared with control group, on day 27 the chimeras in two groups were complete donor type chimeras thereafter to day 70, the MNC count and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD40(+), CD86(+) cells in α-GalCer group were obviously higher than those in control group, at the same time, the hematopoietic reconstitution in α-GalCer group was accelerated as compared with control group. It is concluded that the α-GalCer administration after allogeneic bone marrow transplantations accelerates immune and hematological reconstitution.
Animals ; Bone Marrow Transplantation ; immunology ; methods ; Chimera ; Female ; Galactosylceramides ; pharmacology ; Leukocyte Count ; Lymphocyte Activation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Natural Killer T-Cells ; drug effects ; immunology ; Postoperative Period