Showing papers in "Immunopharmacology and Immunotoxicology in 2002"
TL;DR: Results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.
Abstract: The root of Panax ginseng C. A. Meyer is one of the most popular natural tonics in oriental countries. In this study, we have isolated polysaccharide fraction of Panax ginseng (ginsan) and examined its effect on the function of murine peritoneal macrophages. When macrophages were treated with ginsan, cytotoxic activity against B16 melanoma cells was significantly induced. In addition, the levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and Interferon-gamma (IFN-gamma) were increased and the production of reactive oxygen/nitrogen components such as nitric oxide (NO) and hydrogen peroxide (H2O2) was enhanced. Moreover, phagocytic activity was induced in ginsan-treated macrophages compared to the control. The expression of CD14 and 1-Ab on murine peritoneal macrophages was increased by the treatment with ginsan, while the expression of CD11b was decreased. Taken together, these results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.
176 citations
TL;DR: Evidence is shown that neutrophils express functional vitamin D receptors (VDR) and that 1,25(OH)2D3 has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.
Abstract: 1Alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to modulate the production of various cytokines or the expression of certain differentiation markers in human T cells or monocytes. Its effects on neutrophils, however, are poorly understood. In this paper, we show several lines of evidence indicating that neutrophils express functional vitamin D receptors (VDR). Sort-purified neutrophils from human peripheral blood expressed VDR mRNA at a level comparable to that of monocytes. As reported to occur in monocytes, protein expression of CD14 on the cell surface of neutrophils was augmented when the cells were incubated with 1,25(OH)2D3. To investigate the physiological roles for VDR in neutrophils, we investigated possible modulating effects of 1,25(OH)2D3 on the expression of several genes in lipopolysaccharide-stimulated neutrophils by using differential display analysis. Of the genes we identified, trappin-2/elafin/SKALP, which was originally reported to be an inhibitor of elastase, was induced in neutrophils by lipopolysaccharide, but was suppressed significantly in the presence of 1,25(OH)2D3. Under the same conditions, interleukin-1beta expression was also inhibited. These findings suggest that 1,25(OH)2D3 has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.
113 citations
TL;DR: Chlorogenic acid, a plant polyphenol, inhibited SE-induced T-cell proliferation and production-dates printpubdate="05/03/02" indicate that chlorogenic acid may be therapeutically useful for mitigating the pathogenic effects of SE.
Abstract: Proinflammatory cytokines mediate the toxic effect of staphylococcal exotoxins (SE). Chlorogenic acid, a plant polyphenol, inhibited SE-induced T-cell proliferation (by 98%) and production of interleukin 1beta, tumor necrosis factor, interleukin 6, interferon gamma, monocyte chemotactic protein I (MCP-l), macrophage inflammatory protein (MIP)-lalpha, and MIP-lbeta by human peripheral blood mononuclear cells. These data indicate that chlorogenic acid may be therapeutically useful for mitigating the pathogenic effects of SE. Naturally occurring polyphenolic compounds such as chlorogenic acid may serve as a potent anti-inflammatory agent alternative to conventional chemotherapeutics.
77 citations
TL;DR: It appears that FE represent a reservoir of engulfed CA and rosetting is an efficacious phenomenon of presentation of pathogens to MØ, where an effective clearance of them can take place.
Abstract: The role of fish erythrocytes (FE) as phagocytic cells has poorly been investigated, until now. Here, we have focussed our attention on the interplay between rainbow trout (Salmo gairdneri Richardson) erythrocytes and Candida albicans (CA). At the same time, the intervention of autologous head kidney macrophages (MO) in the CA processing by FE has been studied. Data show that CA particles bind to FE, which, in turn, are able to engulf but not kill them. In the presence of MO, a decrease of FE with bound CA occurs and, in some microscopic images, FE form rosettes with MO. Phagocytosis of CA is higher in rosetting MO than in non-rosetting ones. According to our findings, it appears that FE represent a reservoir of engulfed CA and rosetting is an efficacious phenomenon of presentation of pathogens to MO, where an effective clearance of them can take place.
61 citations
TL;DR: Results indicate that KHT has a good asthma treatment effect, and that its action may be due to the regulation of cytokine production, which is a therapeutic technique that is part of a larger system of traditional oriental medicine.
Abstract: Acupuncture has become quite familiar to many Koreans not only for pain, but also for many other health problems, both in acute and chronic conditions. Actually, acupuncture is a therapeutic technique that is part of a larger system of traditional oriental medicine. There are several styles of acupuncture. We investigated the regulatory effects of cytokine production in peripheral blood of asthma patients (AP) by SOOJI CHIM (Koryo Hand Acupuncture Therapy, KHT). Clinical signs of asthma disappeared markedly by KHT. The mean interleukin (IL)-2 and IL-6 plasma levels were lower in the AP group than in the normal group, whereas the mean interferon (IFN)-gamma, IL-4, and tumor necrosis factor (TNF)-alpha levels were higher in the AP group. Plasma IFN-gamma and IL-2 levels derived from T helper (Th)1 cells and IL-4 levels derived from Th2 cells were elevated in the AP group by KHT. Especially, plasma IL-6 levels derived from Th2 cells were elevated significantly in the AP group by KHT. Reduced plasma levels of TNF-alpha were observed in the AP group by KHT. Plasma IgE levels were also measured but there were no significant differences from each other. During the KHT, there were no other adverse effects. These results indicate that KHT has a good asthma treatment effect, and that its action may be due to the regulation of cytokine production.
51 citations
TL;DR: It is suggested that PI3-kinase may regulate PMA-induced differentiation signal and provide a crucial link between PKC and cAMP in HL-60 cells.
Abstract: Treatment of the human promyelocytic leukemia cell line HL-60 with phorbol myristate acetate (PMA) is associated with induction of monocytic or myelocytic differentiation. Since phosphatidylinositol 3-kinase (PI3-kinase) is a critical player in cell proliferation, survival, and differentiation, we studied the role of PI3-kinase during induction of the differentiated monocytic phenotype and superoxide production. In treatment of HL-60 cells with PMA, the PI3-kinase inhibitors LY294002 and wortmannin inhibited cell adhesion and spreading and phagocytic activity. LY294002 and wortmannin also inhibited the proliferation of HL-60 cells. During PMA-induced monocytic differentiation, LY294002 induced apoptosis in a dose dependent manner. The phosphorylation of p85alpha derived from PMA-stimulated HL-60 cells was shown in the time dependent manner. However, p70 S6 kinase inhibitor, rapamycin, did not inhibit PMA-induced monocytic differentiation. During PMA-induced monocytic differentiation, LY294002 inhibited c-jun protein expression and decrease of c-myc protein level. In contrast, LY294002 induced production of superoxide in the HL-60 cells stimulated with forskolin. Moreover, staurosporine and H7, PKC inhibitors, enhanced superoxide production in dibutyryl cAMP-induced HL-60 cells. These results suggest that PI3-kinase may regulate PMA-induced differentiation signal and provide a crucial link between PKC and cAMP in HL-60 cells.
49 citations
TL;DR: The radioprotective efficacy of AED is accompanied by low toxicity, and a significant improvement in survival was observed at doses as low as 5 mg/kg.
Abstract: We previously showed that one subcutaneous (sc) injection of 5-androstene-3beta,17beta-diol (AED) stimulated the innate immune system in mice and prevented mortality due to hemopoietic suppression after whole-body ionizing irradiation with gamma rays. In the present study, we tested whether there was any significant toxicity in mice that might hinder development of this steroid for human use. There were no indications of toxicity in chemical analyses of serum after sc doses as high as 4000 mg/kg. At this dose, 2 of 54 mice died when given AED alone. When 4800 mg/kg was given orally, no deaths resulted. The only adverse findings attributed to AED administration were 1) a moderate elevation of granulocytes in abdominal organs and fat after sc injections of 320 mg/kg; and 2) occasional wasting of skin over the injection site in female B6D2F1 but not male C3H/HeN mice. Significant weight loss (6%) was observed after sc injections of 320 mg/kg but not 160 or 80 mg/kg. When male C3H/HeN mice were injected sc with AED at doses of 0-200 mg/kg 24 h before whole body gamma-irradiation (9 Gy), a significant improvement in survival was observed at doses as low as 5 mg/kg. Oral administration of AED produced significant survival enhancement at a dose of 1600 mg/kg. We conclude that the radioprotective efficacy of AED is accompanied by low toxicity.
46 citations
TL;DR: It is demonstrated that CVE is a biological response modifier that enhances resistance to Listeria monocytogenes through augmentation of IL-2 and IFN-γ and in normal/non infected mice, it produced no effects in the levels of all cytokines studied.
Abstract: In this study, we have investigated the effects of the unicellular-green-algae Chlorella vulgaris on the production of INF-gamma, IL-2, IL-4 and IL-10 in normal and Listeria monocytogenes infected mice. Our results demonstrated that in normal/non infected mice, CVE administration produced no effects in the levels of all cytokines studied. However, Listeria monocytogenes infection enhanced the production of INF-gamma and IL-2 at 48 and 72 h after the bacteria inoculation. Interestingly, the treatment with five consecutive doses of 50 mg/Kg/day of Chlorella vulgaris given previously to infection, led to further increases in INF-gamma and IL-2 levels at 48 and 72 h in relation to the presence of infection alone. No changes in IL-4 and IL-10 production were observed in Listeria monocytogenes and CVE treated/infected mice. These results are in accordance with the literature, which shows that CVE is a biological response modifier that enhances resistance to Listeria monocytogenes through augmentation of IL-2 and IFN-gamma.
33 citations
TL;DR: The role of IL-1β in the pathological modulation of bone cell metabolism, with regard to implication of the pathogenesis of osteoporosis by IL- 1β, is supported.
Abstract: Interleukin-1β (IL-1β) regulates several activities of the osteoblast cells derived from mouse calvarial bone explants in vitro. IL-1β stimulated cellular proliferation and the synthesis of prostaglandin E2 in the cultured cells in a dose-dependent manner. Furthermore, plasminogen activator activity of the mouse osteoblast was positively affected by IL-1β in a dose-dependent manner over the dosage range of 0.01 ng−2 ng/mL with a maximal effect being observed at 2 ng/mL. However, the induction of osteocalcin synthesis and alkaline phosphatase activity in response to vitamin D, two characteristics of the osteoblast phenotype, were significantly antagonized by IL-1β over a similar dose range.Treatment of mouse calvarial bone cells with IL-1β resulted in a dose dependent stimulation of bone resorption and the bone resorption induced by IL-1β was strongly inhibited by calcitonin treatment, indicating osteoclast-mediated bone resorption, suggesting that the bone resorption induced by IL-1β appears to be...
32 citations
TL;DR: It is suggested that an aqueous extract of Artemisia capillaris THUNB (Compositae) plant (AC) may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.
Abstract: A human hepatoma cell line, Hep G2 cell, is reliable for the study of alcohol-induced hepatotoxicity. In this study, we investigated the effect of an aqueous extract of Artemisia capillaris Thunb (Compositae) plant (AC) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. AC (0.5-5 microg/mL) inhibited the secretion of EtOH-induced interluekin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha). AC also inhibited the EtOH-, IL-1alpha-, and TNF-alpha-induced cytotoxicity. Furthermore, we found that AC inhibited the EtOH-induced apoptosis of Hep G2 cells. These results suggest that AC may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.
31 citations
TL;DR: This review will emphasize on the cytokine and chemokine-mediated signal transductions including the RAS-RAF-mitogen-activated protein kinase (MAPK), Janus kinases (JAK)-signal transducers and activators of transcription (STAT), phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappa B (NF-κB), and various antagonists of receptors and inhibitors of intracellular signaling molecules
Abstract: The incidence and prevalence of allergic diseases such as asthma and allergic rhinitis have recently been increasing worldwide. Eosinophils are the principal effector cells for the pathogenesis of allergic inflammation via the secretion of highly cytotoxic granular proteins including eosinophil cationic protein, major basic protein and eosinophil protein X. Blood and tissue eosinophilia is a common manifestation of late-phase allergic inflammation causing tissue damage. The development of eosinophilia correlates with the production of haematopoietic cytokines including interleukin (IL)-3. IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil-specific chemoattractant, eotaxin, from T-lymphocytes and the epithelium respectively. Elucidation of intracellular mechanisms that control the activation, apoptosis and recruitment of eosinophils to tissues is therefore fundamental in understanding these disease processes and provides targets for novel drug therapy. Over the past decade, there has been intensive investigation for the intracellular signal transduction regulating various biological functions of eosinophils and their roles in the pathogenesis of eosinophil-related diseases. This review will emphasize on the cytokine and chemokine-mediated signal transductions including the RAS-RAF-mitogen-activated protein kinases (MAPK), Janus kinases (JAK)-signal transducers and activators of transcription (STAT), phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappa B (NF-kappaB), and various antagonists of receptors and inhibitors of intracellular signaling molecules as potential therapeutic agents of allergic diseases.
TL;DR: It is suggested that SOAE may be beneficial in the regulation of immediate-type allergic reaction and had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α (TNF-α) production.
Abstract: We investigated the effect of aqueous extract of Sanguisorba officinalis L.(Rosaceae) root (SOAE) on the immediate-type allergic reactions in vivo and in vitro. SOAE (0.01 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. When SOAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SOAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SOAE (0.001 to 1 mg/mL) also dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP (cAMP) in RPMC, When SOAE was added, significantly increased compared with that of normal control. Moreover, SOAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production. These results suggest that SOAE may be beneficial in the regulation of immediate-type allergic reaction.
TL;DR: E ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user, and ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6.
Abstract: The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.
TL;DR: It is suggested that erythrocytes play a role in mediating the inhibitory effects of 1,25(OH)2D3 on IL-8 production-dates printpubdate="05/03/02" in IL-1β-stimulated whole blood.
Abstract: Interleukin (IL)-8, which is involved in inflammatory responses, is produced by a variety of cell types, monocytes/macrophages and neutrophils, in response to inflammatory stimuli including lipopolysaccha ride, IL-1, and tumor necrosis factor α. Here we report the inhibitory effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production-dates printpubdate="05/03/02" in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production-dates printpubdate="05/03/02" in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production-dates printpubdate="05/03/02" induced by IL-1β compared with that induced by tumor necrosis factor α. IL-8 mRNA expression in IL-1β-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1β-induced IL-8 production-dates printpubdate="05/03/02" in whole blood, 1,25(OH)2D3 inhibited IL-8 production-dates printpubdate="05/03/02...
TL;DR: It is shown that vitamin D3 analogue, 1,25(OH)2D3, had a stimulatory effect on ALP activity after 3 days, compared with control, and this finding provides one of signaling pathways for differentiation in primary human osteoblasts.
Abstract: Expression of alkaline phosphatase(ALP)activity represents a key event during the differentiation processes of osteoblasts, and the level of ALP activity has been routinely used as a relative measure of differentiation stages of osteoblasts. In human osteoblasts, we showed that vitamin D3 analogue, 1,25(OH)2D3, had a stimulatory effect on ALP activity after 3 days, compared with control. The treatment of PD098059, an ERK MAP Kinase inhibitor, had a reducing effect on ALP activity, a differentiation marker in 1,25(OH)2D3-treated primary human osteoblasts. However, SB203580, a potent p38 MAP Kinase inhibitor, had no effect on the differentiation in this system. This indicates that ERK, not p38, is directly related to 1,25(OH)2D3-stimulated ALP activity in primary human osteoblasts. These results also show that the vitamin D3 analogue stimulates ERK1 activation in primary human osteoblasts. This finding provides one of signaling pathways for differentiation in primary human osteoblasts.
TL;DR: A significant reduction in thymocytes from newborn and splenocytes from 1-week-old mouse progeny exposed to B[a]P in utero is demonstrated, providing a possible explanation for the relationship between maternal smoking during pregnancy and childhood carcinogenesis.
Abstract: Environmental carcinogen exposure may play an important role in the incidence of cancer in children. In addition to environmental pollutants, maternal smoking during pregnancy may be a contributing factor. Major carcinogenic components of cigarette smoke and other combustion by-products in the environment include polycyclic aromatic hydrocarbons (PAH). Mouse offspring exposed during midpregnancy to the PAH, benzo[a]pyrene (B[a]P), show significant deficiencies in their immune functions, observed in late gestation which persist for at least 18 months. Tumor incidences in these progeny are 8 to 10-fold higher than in controls. We have demonstrated a significant reduction in thymocytes (CD4+ CD8+, CD4+ CD8+ Vbeta8+, CD4+ CD8+ Vgamma2+) from newborn and splenocytes (CD4+ CD8+) from 1-week-old mouse progeny exposed to B[a]P in utero. To investigate possible causes of the observed T cell reduction, we analyzed the thymocytes and splenocytes from progeny and maternal tissues for the presence of B[a]P-DNA adducts. Adducts were detected in maternal, placental and offspring lymphoid tissues at day 19 of gestation, at birth and 1-wk after birth. The presence of B[a]P-DNA adducts in immature T cells may, in part, explain the previously observed T cell immunosuppression and tumor susceptibility in mice exposed to B[a]P in utero. The effects of DNA lesions on progeny T cells may include interference with normal T-cell development. These results provide a possible explanation for the relationship between maternal smoking during pregnancy and childhood carcinogenesis.
TL;DR: Results suggest that YH-Tang may indirectly inhibit TNF-α secretion by inhibiting IL-1 secretion, and indicate that Yh-Tang has regulatory effects on cytokine secretion in an acute CI patient.
Abstract: Yuldahansotang (YH-Tang), a Sasang Constitutional prescription composed of seven herbal mixtures, has been developed as a formula to prevent and treat cerebral infarction (CI) of Taeumins. However, the mechanisms by which this formula affects CI remain unknown. Previously, regulation of serum cytokine levels by YH-Tang has been observed in individuals at the acute stage of CI disease. It is uncertain whether this is a cause or a result of the disease process. In this study, we investigated whether YH-Tang inhibited secretion of inflammatory cytokines from human astrocytes. YH-Tang regulated the cytokine secretions in astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). YH-Tang significantly inhibited interleukin (IL)-1, IL-4, IL-6 and tumor necrosis factor-alpha (TNF-alpha) secretion in astrocytes stimulated with SP and LPS, but did not inhibit interferon-y (IFN-gamma) and IL-2 secretion significantly. IL-1 has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Therefore, we investigated whether IL-1 mediated inhibition of TNF-alpha secretion from astrocytes by YH-Tang. Incubation of human astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that YH-Tang may indirectly inhibit TNF-alpha secretion by inhibiting IL-1 secretion. Moreover, these findings indicate that YH-Tang has regulatory effects on cytokine secretion in an acute CI patient.
TL;DR: The results suggest that BHT modulates antigen-specific immune responses, and might be used as a therapeutic agent for patients who need enhanced immune function.
Abstract: Bo-yang-hwan-o-tang (BHT) has long been used to treat cancer in traditional Korean medicine and is believed to have immune-modulating activity. This study investigated the effect of BHT on the induction of antigen-specific immune responses using hen egg-white lysozyme (HEL) as a model antigen system. Oral administration of BHT enhanced both HEL-specific humoral and lymphocyte proliferative responses in HEL low-responder mice. Feeding BHT to the mice increased INF-γ levels, but did not change IL-4 levels. Interestingly, however, the oral BHT feeding significantly increased HEL-specific antibodies of the IgG1, IgG2b, and IgG3 subtypes, which are associated with the direct stimulation of B cells. This indicates that BHT treatment enhances anti-HEL-specific humoral immune responses via the direct stimulation of B lymphocytes rather than by selective priming of specific subtypes of the helper T-cell population. This conclusion was supported by in vitro experiments, in which the presence of BHT signific...
TL;DR: The results indicate that SPAE may possess strong antiallergic activity and suggest that differences in bioavailability may cause differential activity following different administration routes.
Abstract: The effect of aqueous extract of Salvia plebeia R. Brown (Labiatae) (SPAE) on the mast cell mediated immediate-type allergic reactions in rats was studied. SPAE (0.05 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. SPAE (0.001 and 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally, intraveneously or orally administered. When SPAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SPAE (0.001 to 1 mg/mL) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when SPAE (0.1 and 1 mg/mL) was added, significantly increased compared with that of basal cells. Moreover, SPAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α (TNF-α production. These results indicate that SPAE may possess s...
TL;DR: In this paper, the authors showed that UPLE alone did not induce GM-CFC colony growth, i.e., had no colony-stimulating activity (CSA), while sera of mice treated with UPLE p.o. or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells in the bone marrow of normal or sublethally irradiated mice.
Abstract: Ultrafiltered pig leukocyte extract (UPLE, IMUNOR®, ImunomedicA, Usti nad Labem, Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and increased survival of mice exposed to a lethal radiation dose. In experiments in vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony formation in cultures of normal mouse bone marrow cells, i.e., produced colony-stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e., had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were added to bone marrow cultures containing suboptimal concentration of recombinant mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM-CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced co-stimulating activity (CoSA). Based on the findings obtained ...
TL;DR: It is suggested that low levels of ethanol consumption can differentially modulate immune cells in thymus, spleen, bone marrow and liver, which may be due to differential regulation of STAT5 activation by ethanol.
Abstract: Ethanol has been recognized as an immunosuppressive agent for many years. Effects of high levels of ethanol consumption on immune functions have been extensively studied, but little is known about the effects of low levels (scuh as 5% ethanol) of ethanol consumption. Herein we report that exposure of mice to 5% ethanol for 4–8 weeks decreases IL-2-augmented splenic NK cell activity, decreases the numbers of NK cells in spleen and liver, decreases the number of granulocytes (Gr-1+) in bone marrow and spleen, and decreases the percentages of B cells in liver. In contrast, the percentages of CD4+CD8+ thymocytes, CD4+CD8− splenocytes, CD4+CD8− liver nonparenchymal cells, CD3+ splenocytes, and CD3+ bone marrow cells were increased. Furthermore, exposure to 5% ethanol increases STAT5 activation in T cells and liver cells while decreases STAT5 activation in NK cells. Taken together, these findings suggest that low levels of ethanol consumption can differentially modulate immune cells in thymus, spleen, b...
TL;DR: The results suggest that A. australe may exert effects on myelopoiesis that may be implicated in antitumor immune responses, which could affect survival of tumor-bearing mice.
Abstract: Previous studies on the Ehrlich ascites tumor (EAT) model indicate that tumor progression is associated with reduced myelopoiesis and increased extramedullar hematopoiesis. In order to investigate the in vivo antitumor activity of Acanthospermum australe, its hydroalcoholic extract was partitioned with different solvents and the resulting extracts were monitored by their effects on bone marrow and spleen hematopoietic progenitor cell proliferation and differentiation in EAT-bearing mice. Oral treatment of tumor-bearing mice with 3 doses of 100, 500 and 1000 mg/kg of the crude hydroalcoholic extract and its chloroformic, butanolic and aqueous fractions significantly stimulated myelepoiesis and brought extramedullar hematopoiesis back to near control values. In normal mice, stimulation of myelopoiesis was only observed with the crude and the butanolic extracts. All the extracts at 500 mg/kg significantly increased survival of tumor-bearing mice, however a clear survival advantage in the group treate...
TL;DR: Biphalin and one of its analogs stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production-dates printpubdate="05/03/02".
Abstract: The opioid pentapeptides called enkephalins were originally described as the endogenous ligands for the opioid receptors. Although their precise physiological significance still remains elusive, the enkephalins have been reported to exhibit analgesic, antidepressant, antianxiety and anticonvulsant activities. In addition, enkephalins have also been shown to act as immunomodulator. The first generation of dimeric peptides was derived from enkephalins. Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent opioid analog containing two tyrosine residues. We have evaluated the immunomodulatory properties of biphalin and its analogs in various in vitro tests. We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production. Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes. Furthermore, these peptides inhibited tumor necrosis factor (TNF-alpha) production in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) and nitric oxide (NO) production in mouse macrophage cells, RAW 264.7. Our observations suggest immunomodulatory property of biphalin and its analog.
TL;DR: The data clearly indicated that the diminished B cell proliferation in ethanol-consuming mice was due in part to an excessive amount of IL-4 produced and an inability of the B cell to interact properly withIL-4 that was secreted by helper T cells.
Abstract: We and others have demonstrated that ethanol suppresses the antibody response in humans and animals. The purpose of this study was to determine whether ethanol affects cytokine-induced proliferative responses of splenic B blast cells, and whether the decreased response was due to an imbalance of the cytokine activity. Thus, the ability of spleen cells from individual ethanol-diet-fed C57BL/6 mice to proliferate and produce cytokines was determined. The ability of anti-IgM monoclonal antibodies (mAb)-activated splenic B blast cells in response to mouse recombinant IL-2 (rIL-2) or rIL-4 was also assessed. A thymidine incorporation assay was used to determine cell proliferation, and the conventional bioassays for cytokine-dependent cell proliferation were used for determining the bioactivity of cytokines. Data were analyzed with general linear model procedure.Our results showed that ethanol weakened the proliferative response of B cells in response to mitogen as well as to mouse rIL-2 and rIL-4. The ...
Journal Article•
TL;DR: In Salmo gairdneri Richardson trouts, a comparison was made between macrophages derived from head kidney and peripheral blood monocytes, and the ability of trout erythrocytes to engulf Candida albicans was evaluated and compared to the MO phagocytosis.
Abstract: In Salmo gairdneri Richardson trouts, a comparison was made between macrophages (MO) derived from head kidney and peripheral blood monocytes Morphologically and cytochemically no differences were observed between these two types of mononucleated cells On the other hand, in parallel studies the ability of trout erythrocytes to engulf Candida albicans (CA) was evaluated and compared to the MO phagocytosis In erythrocytes, engulfment is preceded by binding to CA and cell membrane invagination, while this was not the case for MO Finally, MO stimulated with lipopolysaccharides (LPS) did not modify their phagocytic capacities, thus suggesting a lack of LPS receptors or a tolerance to LPS
TL;DR: Results showed that diHDA-glycerol induced a rapid NF-κB translocation as a consequence of IκB-α proteolysis, and induced a strong activation of neutral sphingomyelinase, suggesting an important role of sphingolipids in the regulatory responses induced by diH DA- glycerol.
Abstract: The use of non specific immunomodulatory agents takes an important place in the aspecific host response to invading microorganisms. In this context, antimicrobial properties of royal jelly have been ascribed to organic acids (mainly 10 hydroxy-2-decenoic acid or 10-HDA) and proteins. We synthesized a derivative of 10-HDA, the 1-(2-methoxyethoxymethyl)2,3-(10-hydroxy2-decenoyl)(E) glycerol referred as diHDA-glycerol which was previously found to protect mice against virulent Salmonella typhimurium challenge through more adequate immune regulations. This study was conducted to further investigate some of the signaling pathways followed by diHDA-glycerol in cell transduction. Members of NF-kappaB transcription factors are key regulators of many cytokines acting on immunity and they control genes involved in responses to numerous signals such as bacterial products. Therefore, we investigated some parameters acting on NF-kappaB translocation in U937 cells after diHDA-glycerol treatment. Due to the chemical structure of the molecule we also investigated the sphingomyelinase pathway. Our results showed that diHDA-glycerol induced a rapid NF-kappaB translocation as a consequence of IkappaB-alpha proteolysis. An intracellular production of reactive oxygen species (ROS) may also account for NF-kappaB activation, without de novo protein synthesis. DiHDA-glycerol induced a strong activation of neutral sphingomyelinase, suggesting an important role of sphingolipids in the regulatory responses induced by diHDA-glycerol.
TL;DR: The current state of knowledge concerning latex allergy is reviewed, including the clinical spectrum, identified allergens, the cross-reactions regarding the latex-fruit syndrome, diagnostic procedures and preventive measures.
Abstract: Latex allergy is an increasingly common condition, because use of latex products is widespread. The reactions to latex manufactures can be classified as allergic and non-allergic, these are the most common. Latex proteins are responsible for immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from rhinitis, conjunctivitis and urticaria to anaphylactic shock. Chemical additives can cause allergic contact dermatitis. The clinical symptoms of latex allergy could arise from direct contact with latex products, but may also result from inhalation of airborne allergens. Subpopulations at particular risk include: atopics, children with spina bifida or individuals who required frequent surgical instrumentations, health care workers, and all persons who have regular contact with latex products. Diagnosis of allergy is based initially on history: search for specific serum IgE, skin prick test and provocation test may confirm the suspicion. The most effective strategy in the treatment of latex allergy is avoidance, however this is virtually impossible, given large number of latex products we encounter since childhood. In this paper we review the current state of knowledge concerning latex allergy, including the clinical spectrum, identified allergens, the cross-reactions regarding the latex-fruit syndrome, diagnostic procedures and preventive measures. Several personal data increase awareness on this issue.
TL;DR: Mite Dpt and Df were the most common causative agents of allergic rhinitis in the Lebanese group studied and determination of all the parameters studied in conjunction appears to be of diagnostic value.
Abstract: Background: Hitherto immunological determinates in Lebanese patients with rhinitis have not been investigated.Objective: To identify causative allergens in Lebanese patients with allergic rhinitis and determine possible correlation's among serum allergen specific antibody, polyclonal IgE, IL-4, IL-5 and peripheral eosinophil levels.Methods: One hundred and thirteen patients with a long lasting history of nasal obstruction, rhinorrhea, sneezing and nasal itching were investigated. Serum allergen specific antibodies using a panel of 10 potential allergens, IL-4 and IL-5 levels were determined by enzyme immunoassays. Polyclonal IgE levels were estimated by an immunochromatographic assay and eosinophil counts by a Coulter STKS counter.Results: Based on the presence of serum allergen-specific IgE antibodies, 74 patients were considered to have an allergic etiology. Polyclonal IgE levels were elevated in 41 of the 74 allergic rhinitis patients while the other 33 patients had normal serum levels. In the ...
TL;DR: In this paper, the effects of human recombinant interleukin-2 (rIL-2) on the lupus disease of (NZB×NZW) F1 mice was observed as no change in the following parameters, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production.
Abstract: The exacerbation of pre-existing autoimmune diseases is a potential toxic effect of immunoactive drugs. An increase in the incidence of autoimmune thyroiditis has been noted in patients treated with human recombinant interleukin-2 (rIL-2). In contrast, human rIL-2 tends to protect mice from autoimmunity. As the effects of murine rIL-2 on autoimmunity have not been reported in mice, lupus-prone female (NZB×NZW) F1 mice were treated with 20,000 IU murine rIL-2 intraperitoneally, twice weekly for 13 weeks, beginning at 15 weeks of age. No evidence of an exacerbating effect of murine IL-2 on the lupus disease of (NZB×NZW) F1 mice was observed as no change in the following parameters were seen, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production. These results show that: 1) like human rIL-2, murine rIL-2 does not exacerbate autoimmunity in mice; 2) the biological effects of human as well as murine rIL-2 in mice differ from those seen with human rIL-2 in man. These ...
TL;DR: The results show that the pattern of lamellipodial extensions of the cell membrane is not entirely randomly-designed, but it is partly regulated by deterministic components, as revealed by the presence of statistically significant periodicities.
Abstract: fMLP (N-formyl-methionyl-leucyl-phenylalanine) is a powerful activator of granulocytes, eliciting different metabolic responses, such as generation of reactive oxygen species, production-dates printpubdate="05/03/02" of arachidonic acid metabolites, and release of lysosomal enzymes. fMLP determines also a dramatic rearrangement of the actin cytoskeleton; under non-gradient conditions this entails characteristic alterations in cell shape (chemokinesis), while under gradient conditions it is instrumental in promoting cell migration up the gradient (chemotaxis). Here we analyze mathematically the cell contour of fMLP-stimulated human granulocytes stimulated with fMLP under non-gradient conditions, using the methods for study of stochastic series. The cell contours were drawn and divided into 200 segments of equal linear length and the angles between consecutive segments were computed. The derived series of angles were examined for autocorrelations and from the autocorrelation function the power spect...