The Protective effect of vitamin E and selenium against peroxidative damage in white blood cells was studied. Forty-eight male rats (~100g BW) were divided into four groups and were fed with a torula yeast based diet deficient in Vit.E and Se. Vit.E (100IU/Kg diet) and Se (0.3ppm) supplementation increased the total peritoneal cell (P.C) population and cell survival rate. Selenium supplementation decreased the hydrogen peroxide generation (half of the control) significantly and Vit.E supplementation reduced the malonaldehyde production during phagocytosis in vitro. However, superoxide generation was not affected by the supplementation of Vit.E or Se. There were no significant differences in catalase activity between groups but glutathione peroxidase activity was increased about twofold by Se supplementation with no effect of Vit.E. In a separate experiment, activated alveolar macrophages were obtained from BCG infected rabbits fed a diet supplemented with Vit.E (100 IU/Kg diet) or Se (0.3 ppm). Se supplementation increased glutathione peroxidase in cells, and both Vit.E and Se increased the cell survival rate during phagocytosis as compared to the control. Both Vit.E and Se are necessary to protect host cells from peroxidative damage during phagocytosis.
Animal ; Macrophages/drug effects ; Macrophages/physiology* ; Male ; Peroxides/metabolism* ; Phagocytosis/drug effects* ; Rats ; Selenium/pharmacology* ; Vitamin E/pharmacology*

Polysaccharides extracted from various sources are natural active substances, which may lead to the activation of macrophage via multiple pathways and mechanisms. This article intends to illustrate the signaling pathways of polysaccharides from plants, fungi, algae and other sources, to identify the mechanisms on the molecular level, and to explore the novel target immunomodulatory agents.
Animals ; Humans ; Macrophage Activation ; drug effects ; immunology ; Macrophages ; drug effects ; immunology ; metabolism ; Polysaccharides ; pharmacology ; Signal Transduction

Astragalus membranaceus ; chemistry ; Cell Line ; Cytokines ; metabolism ; Humans ; Inflammation ; Macrophages ; drug effects ; metabolism ; Monocytes ; drug effects ; metabolism ; Polysaccharides ; pharmacology

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T. gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of proand anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of IL-12, TNF-alpha, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-alpha expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii lysate triggered nuclear factor (NF)-kappaB-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T. gondii lysate treatment might occur via TLR2-mediated NF-kappaB activation.
Animals ; Cell Line ; Cytokines/*biosynthesis ; Humans ; Inflammation/metabolism ; Lipopolysaccharides/*pharmacology ; Macrophages/*drug effects/*metabolism ; Toxoplasma

Animals ; Beverages ; Macrophages ; drug effects ; metabolism ; Mice ; Mice, Inbred Strains ; Receptors, Complement 3b ; metabolism

Bronchoalveolar Lavage Fluid ; Humans ; Interleukin-1beta ; metabolism ; Macrophages, Alveolar ; cytology ; drug effects ; metabolism ; Silicon Dioxide ; adverse effects ; Silicosis ; metabolism

OBJECTIVETo investigate the effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in human macrophages and the membrane potential and foaming process of the macrophages.

METHODSThe effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in cultured human monocyte-derived macrophages was investigated using real-time RT-PCR and Western blotting, and its effect on the membrane potential was analyzed with optical mapping of the membrane potential with voltage-sensitive dyes. The ratio of cholesterol ester (CE) in the macrophages following intake of oxidized low-density lipoprotein (OxLDL) was analyzed by an enzymatic fluorometric method.

RESULTSThe expression of Kv1.3 and Kir2.1 channels in the macrophages were down-regulated by diclofenac (1.5 µmol/L and 15 µmol/L). Compared with those in the control group, Kv1.3 mRNA expression was reduced by over 80% and 90% (P<0.05), and Kir2.1 mRNA by over 20% and 30% (P>0.05), respectively; both their protein expression was reduced by over 10% and 60% with a dose- dependent effect (P<0.05). Diclofenac at the two doses dose-dependently reduced the surface fluorescence intensity of the macrophage, and the membrane potential was decreased by 28% and 54%, respectively (P<0.05). Incubation of the macrophages with 30 mg/L OxLDL for 60 h caused an obvious enlargement of the cell volume and deposition of numerous lipid granules in cytoplasm, resulting also in a CE/TC ratio over 50% (P<0.05). Diclofenac at 1.5 and 15 µmol/L both significantly decreased the CE/TC ratio to (23.624∓3.34)% and (13.601∓2.916)% (P<0.05), respectively, but this effect did not show a dose-response relationship (P>0.05).

CONCLUSIONDiclofenac can significant down-regulate the expression of Kv1.3 and Kir2.1 channels in human macrophages, lower their membrane potential and inhibit the process of foam cell formation.

Cells, Cultured ; Diclofenac ; pharmacology ; Foam Cells ; cytology ; drug effects ; Humans ; Kv1.3 Potassium Channel ; metabolism ; Macrophages ; drug effects ; metabolism ; physiology ; Membrane Potentials ; drug effects ; Potassium Channels, Inwardly Rectifying ; metabolism

OBJECTIVETo study the effect of total glucosides of paeony (TGP) on lipopolysaccharides (LPS)-induced nuclear factor-kappaB (NF-kappaB) activation in macrophages.

METHODRat peritoneal macrophages were pre-treated with TGP for 2 h and stimulated with LPS for 20 min or 0.5 h. Inhibitory kappaBalpha (IkappaBalpha) protein in the cytoplasm and NF-kappaB p65 protein in the nuclear were analyzed by western blot. Further, DNA binding activity of NF-kappaB complex was detected.

RESULTTGP enhanced the amounts of IkappaBalpha protein in the cytoplasm and decreased the amounts of NF-kappaB p65 protein in the nuclear of LPS-induced macrophages. TGP also inhibited the LPS-mediated DNA binding activity of NF-kappaB complex in macrophages.

CONCLUSIONTGP can inhibit LPS-induced NF-kappaB activation in macrophages through arresting IKBalpha protein degradation, NF-kappaB p65 protein nuclear translocation and DNA binding activity of NF-kappaB complex.

Animals ; Cell Nucleus ; drug effects ; metabolism ; Cytoplasm ; drug effects ; metabolism ; DNA ; metabolism ; Dose-Response Relationship, Drug ; Glucosides ; pharmacology ; Macrophages, Peritoneal ; cytology ; drug effects ; metabolism ; NF-kappa B ; metabolism ; Paeonia ; chemistry ; Protein Transport ; drug effects ; Rats ; Transcription Factor RelA ; metabolism

BACKGROUNDThe immunomodulatory effects of glucocorticoids (GCs) have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immunosuppressive mechanisms of GCs have been investigated intensely, the immunopermissive effects of GCs remain unclear. A lot of studies showed GCs could exert rapid non-genomic actions. We herein studied the rapid immunopromoting effects of GCs.

METHODSWe observed the rapid (within 30 minutes) effects of corticosterone on respiratory burst of mouse peritoneal macrophages and studied their mechanisms. The superoxide anions were measured by cytochrome C reduction assay. Protein kinase C phosphorylation was measured by Western blotting and membrane fluidity was evaluated by fluorescence polarization measurement.

RESULTSThe 10(-8) mol/L and 10(-7) mol/L corticosterone rapidly increased the superoxide anions production by macrophages, which were insensitive to GC-receptor antagonist, mifepristone, and protein-synthesis inhibitor, cycloheximide. Corticosterone coupled to bovine serum albumin was able to mimic the effects of corticosterone. The effects were independent of protein kinase C pathway and the change in membrane fluidity.

CONCLUSIONSThe results indicate that corticosterone rapidly promote the superoxide anions production by mouse peritoneal macrophages may through non-genomic mechanisms. This study may contribute to understanding the effects of GCs under stress condition and the physiological significance of nongenomic effects of GCs.

Animals ; Corticosterone ; pharmacology ; Macrophages, Peritoneal ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Respiratory Burst ; drug effects ; Superoxides ; metabolism

OBJECTIVETo study the effect of SiO(2) on the expression of platelet derived growth factor (PDGF) in human silicotic alveolar macrophages (AM) and human embryonic lung fibroblasts (HELF).

METHODSHuman alveolar macrophages were collected from a silicotic patient by bronchoalveolar lavage and exposed to SiO(2) for 3, 6, 12, 18, 24 and 36 h. The cultured supernatant at 24 h was incubated with human embryonic lung fibroblasts for 6, 12, 18, 24, 36 and 48 h. The immunocytochemistry and Western blot were used to detect the level of expression of PDGF in lung fibroblasts and their supernatant respectively. (3)H-proline was used to detect the synthesis and secretion of collagen in HELF.

RESULTSThe expression of the PDGF in the supernatant of alveolar macrophages exposed to SiO(2) increased significantly and reached the peak at 24 h (average optical density: 0.282 +/- 0.019 vs 0.214 +/- 0.014, P < 0.01) with ELISA. The expression of PDGF in lung fibroblasts and their supernatant increased at different time (6, 12, 18, 24, 36 and 48 h) with immunocytochemistry and Western blot respectively when incubated with the cultured supernatant of silicotic AM exposed to SiO(2). The expression of PDGF was significantly different from the control group (P < 0.05). The synthesis and secretion of collagen in FB were increased markedly when incubated with the cultured supernatant of AM stimulated by SiO(2) compared with the control group.

CONCLUSIONSiO(2) may affect the expression of PDGF and synthesis of collagen through AM mediation and participate in the formation of lung fibrosis.

Cells, Cultured ; Collagen ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Humans ; Macrophages, Alveolar ; drug effects ; metabolism ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; metabolism ; Silicon Dioxide ; pharmacology