Showing papers in "Immunopharmacology and Immunotoxicology in 2008"
TL;DR: Results show that amentoflavone treatment reduces experimental tumor metastasis and suggest that such an action is associated with attenuation of tumor invasion, proliferation and angiogenesis.
Abstract: Amentoflavone has been shown to inhibit tumor metastasis in vivo, but its mechanism of action remains unclear. Here, C57BL/6 mice were injected once with B16F-10 melanoma cells via tail vein followed by amentoflavone treatment (50 mg/kg BW) for 10 consecutive days. Twenty-one days after tumor injection, animals were euthanized, and tumor metastasis was found to confine in the lungs. As compared with the tumor controls, amentoflavone treatment significantly lowered the number of lung nodules (p<0.001). Amentoflavone treatment markedly decreased the mRNA expression of MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, TNF-alpha, IL-1beta, IL-6, and GM-CSF in lung tissues. However, amentoflavone treatment increased the mRNA expression of STAT-1 and nm23 in lung tissues. Also in vitro studies indicate that amentoflavone treatment inhibits tumor cell invasion and migration. These results show that amentoflavone treatment reduces experimental tumor metastasis and suggest that such an action is associated with attenuation of tumor invasion, proliferation and angiogenesis.
88 citations
TL;DR: The findings suggest that the immunomodulatory and anti-cancer effects of this new formula (PSP+APS) were better than those of PSP alone, and also could resist immunosuppression induced by AMD.
Abstract: The aim of this study was to determine whether polysaccharopeptide (PSP) and Astragalus polysaccharides (APS) can be combined together as a new complex prescription (PSP + APS) for aiding adriamycin (AMD) chemotherapy. Ehrlich's ascites carcinoma (EAC) was used to establish a solid tumor model in Kunming mice. Immunocytochemical and immunohistochemical analysis were employed to detect the immunoregulatory and anti-tumor effects of EAC bearing mice after 30 days of administration with PSP and APS. PSP and PSP + APS could significantly increase the percentage of CD3(+) and CD4(+) T-lymphocytes, the ratio of CD4(+)/CD8(+), and the expression of IL-2/IL-2R in spleen and Bax in tumor tissue, but led to a diminution of Bcl-2 and CDK4 in tumor tissue compared with those of control group. In addition, PSP +APS could restore the immunological effects against AMD-induced immunosuppression, such as the subset of leukomonocyte, the expression of IL-2/IL-2R in the spleen, and the thymus index. These findings suggest that the immunomodulatory and anti-cancer effects of this new formula (PSP+APS) were better than those of PSP alone, and also could resist immunosuppression induced by AMD.
69 citations
TL;DR: The kaempferol improved the post-ischemic LVEDP and LVDP significantly after 20, 30, 40 and 50 min of reperfusion compared with the untreated control hearts, which shows that kaEMPferol offers protection against I/R-associated cardiac dysfunction.
Abstract: This study examined whether or not the ER stress and Bcl-2 proteins are linked to the protective effect of kaempferol, a phytoestrogen, on ischemia-reperfusion (I/R)-induced cardiac damage. In order to determine if kaempferol modifies the I/R-induced response in H9c2 cardiac muscle cells, the cells were exposed to kaempferol followed by ischemia 12h/reperfusion 4h. kaempferol had a protective effect on the apoptosis induced by I/R in the cardiac muscle cells. The Kaempferol treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased the level of the pro-apoptotic protein, bax. Kaempferol down-regulated the expressions of the endoplasmic reticulum (ER) stress proteins, GRP78, ATF-6alpha, XBP-2, IRE1-alpha, phosphor-eIF-2alpha and CHOP. In ex vivo-Langendorff experiment, the kaempferol treatment regulated the expression of ER stress proteins-CHOP and GRP78. The kaempferol also improved the post-ischemic LVEDP and LVDP significantly after 20, 30, 40 and 50 min of reperfusion compared with the untreated control hearts, which shows that kaempferol offers protection against I/R-associated cardiac dysfunction.
59 citations
TL;DR: Results demonstrated an augmented expression of both CD14 and TLR4 in the substantia nigra of mice treated with MPTP in comparison to untreated animals, suggesting that the endotoxin receptors are over expressed in different manner in specific areas of the CNS during Parkinson's-like disease.
Abstract: Systemic infections are often associated with neurodegenerative processes in many diseases of the central nervous system (CNS), including Parkinson's disease. Toll-like receptor (TLR)4 and CD14 act as receptors for lipopolysaccharide (LPS) released by gram-negative bacteria. In this contest, CD14 functions as the main LPS ligand and TLR4 transmits the LPS signal into the cell. In this paper, we investigated the expression of TLR4 and CD14, in different anatomical areas of the CNS, in an experimental model of Parkinson's-like disease, represented by MPTP-treated mouse. In particular, we analyzed the gene transcripts and proteins expression of CD14 and TLR4, in the substantia nigra and caudate-putamen nuclei of these animals. Results demonstrated an augmented expression of both CD14 and TLR4 in the substantia nigra of mice treated with MPTP in comparison to untreated animals, suggesting that the endotoxin receptors are over expressed in different manner in specific areas of the CNS during Parkinson's-like disease.
58 citations
TL;DR: It is found that oral EP reduces bacterial burden during infection by Listeria monocytogenes, demonstrating its efficacy in vivo, and an endotoxin-free EP extract activates the innate immune response, stimulating production of IL-6, TNF, IL-12 and NO from macrophages in vitro.
Abstract: Public interest in Echinacea is growing rapidly. Unfortunately, there is little scientific evidence to support claims of efficacy of this widely used botanical, and little information about potential mechanism of action. This study examines the ability of Echinacea to upregulate macrophage function and begins to elucidate the mechanism of Echinacea-induced macrophage activation. Murine peritoneal macrophages were cultured with E. purpurea extracts enriched for plant polysaccharide (EP). ELISA was used to measure cytokine production. MAPKs were blocked using specific inhibitors, and Western blotting used to identify phosphorylated proteins involved in signal transduction. To examine in vivo efficacy, EP was administered orally and Listeria monocytogenes given i.v. Mice were sacrificed three days post-infection to determine bacterial load in the spleen. We demonstrate that an endotoxin-free EP extract activates the innate immune response, stimulating production of IL-6, TNF, IL-12, and NO from macrophages in vitro. Along with evidence of enhanced macrophage function, we found that oral EP reduces bacterial burden during infection by Listeria monocytogenes, demonstrating its efficacy in vivo. EP initiates a signaling cascade within macrophages through both TLR4-dependent and -independent mechanisms, involving ERK, p38 and JNK, and ultimately the activation of NF-kappaB.
56 citations
TL;DR: Findings demonstrate that in addition to the vasodilation and neuromodulation activity of H2S, it may contribute to the pathogenesis of inflammatory diseases via regulating the activation of leukocytes.
Abstract: Accumulating evidence has suggested that hydrogen sulfide (H2S) is endogenously generated in many types of mammalian cells. Since H2S plays an important role in cardiovascular, central nervous and gastrointestinal systems, it is currently considered to be the third gaseous mediator. Recently, more and more attention has been paid to the biological functions of H2S in inflammation. In various animal models of inflammatory diseases (such as acute pancreatitis, sepsis and endotoxemia), endogenous H2S has been shown to be overproduced and participate in regulating the severity of inflammatory response and associated organ injury. Inhibition of H2S formation is likely to protect animals against these inflammatory diseases. H2S may exert its effect on inflammation via regulating the function of leukocytes, leukocyte trafficking and immune cell survival. Furthermore, H2S has been suggested to induce the release or production of neuropeptides (substance P and calcitonin gene-related peptide), which are considered...
47 citations
TL;DR: The present study revealed that the food material Hsp-G was effective when administered with standard anti-rheumatoid therapy in ameliorating RA in mice and humans without any adverse effects and may improve the quality of life for patients with RA as a complementary/alternative medicine.
Abstract: Hesperidin (Hsp) is an abundant flavonoid in citrus fruits, and the oral administration of Hsp has been recently reported to suppress collagen-induced arthritis in mice. Therefore, we sought to determine whether alpha-glucosylhesperidin (Hsp-G), which is an Hsp derivative with enhanced water-solubility, is effective on treating arthritis in both mice and humans. Hsp-G was orally administered to mice with collagen-induced arthritis, and its effects were evaluated clinically and histologically. Oral administration of Hsp-G improved collagen-induced arthritis when administered before the onset of arthritis as well as when administered after its onset. A decrease in tumor necrosis factor-alpha production was found to cause this improvement. In the human study, 19 patients with rheumatoid arthritis (RA) were enrolled in a 12-week double-blind, placebo-controlled trial. Patients were administered beverages containing 3 g Hsp-G (n = 9) or placebo (n = 10) every morning for the duration of the 3-month trial. Additionally, patients received standard therapy from a physician every 4 weeks. As a result, 3 of 9 patients in the Hsp-G group improved, while only 1 of 10 patients in the placebo group improved; this was in accordance with the American College of Rheumatology criteria. The present study revealed that the food material Hsp-G was effective when administered with standard anti-rheumatoid therapy in ameliorating RA in mice and humans without any adverse effects and may improve the quality of life for patients with RA as a complementary/alternative medicine.
43 citations
TL;DR: The results suggest that tanshinone can be a good marker compound to explain the antiosteoporotic function of SM and suggest that there are other unknown compounds in the SM extract that have a synergistic effect with tansinone.
Abstract: Tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone are compounds that have been isolated from the root of Salvia miltiorrhiza (SM), which is also known as "Danshen." The SM extract has been used successfully in China for treating postmenopausal syndrome. Furthermore, it was previously reported that SM had inhibitory effect on osteoporosis in ovariectomized rats. Another study reported that the four components, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone, prevented osteoclast function in an in vitro system. However, there are no reports of a correlation between SM and its components on osteoporosis and osteoclast function. This study was undertaken to examine the effect of SM on osteoclastogenesis and osteoblast differentiation, which are two important markers of the bone physiology. Through a rapid, sensitive and specific isocratic liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of four diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone in SM, the authors tried to correlate the amount of tanshinone compounds in SM into the antiosteoclast activity. The SM fraction (methanol and ethanol isolated) with a low concentration of tanshinone IIA (1 mug/mL) had no effect on the alkaline phosphotase activity (osteoblast differentiation), but completely inhibited osteoclastogenesis. Although the tanshinone compound itself showed similar effects, the concentrations of commercially available tanshinone (diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone) needed for antiosteoclast activity was almost 1000 times more than that of tanshinone in SM fraction. This suggests that there are other unknown compounds in the SM extract that have a synergistic effect with tanshinone. These results also suggest that tanshinone can be a good marker compound to explain the antiosteoporotic function of SM.
37 citations
TL;DR: It is reported here that, in TNF-α-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-κB and the accumulation of lipid rafts was inhibited by the flavonoids.
Abstract: Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating the production of cytokines, such as tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). However, their mechanisms of action are not fully understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll-like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the inhibitor of κB (IκB), with resultant activation of nuclear factor-κB (NF-κB), but also the phosphorylation of p38 and Akt in bone marrow-derived macrophages that have been stimulated with LPS. We report here that, in TNF-α-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-κB. Accumulation of lipid rafts, the initial step in the signaling pathway, was significantly inhibited when macrophages were treated with QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid rafts was inhibited by the flavonoids when B cells were activated via the membrane IgM...
37 citations
TL;DR: Natural inhibitors of snake venoms play a significant role in the ability to neutralize the degradation effects induced by venom toxins as discussed by the authors, and the biomedical value of these natural inhibitors can lead to the development of new therapeutics for an assortment of diseases as well as contributing to efficient antivenoms for the treatment of ophidic accidents.
Abstract: Natural inhibitors of snake venoms play a significant role in the ability to neutralize the degradation effects induced by venom toxins. It has been known for many years that animal sera and some plant extracts are competent in neutralizing snake venoms. The purpose of this review is to highlight the recent work that has been accomplished with natural inhibitors of snake venoms as well as revisiting the past research including those found in plants. The biomedical value of these natural inhibitors can lead to the development of new therapeutics for an assortment of diseases as well as contributing to efficient antivenoms for the treatment of ophidic accidents.
32 citations
TL;DR: Intraperitoneal administration of ursolic acid and glycyrrhizic acid (50 μmoles/Kg body wt for 5 consecutive days) was found to produce increased natural killer cell activity (NK-activity) in metastatic tumor-bearing animals.
Abstract: Effect of terpenoids, ursolic acid and glycyrrhizic acid on the cell-mediated immune response was studied in metastatic tumor-bearing C57BL/6 mice Intraperitoneal administration of ursolic acid and glycyrrhizic acid (50 μmoles/Kg body wt for 5 consecutive days) was found to produce increased natural killer cell activity (NK-activity) in metastatic tumor-bearing animals In the glycyrrhizic acid- and ursolic acid-treated groups the peak activity was observed on the 4th day (602% and 43% cell lysis respectively) Whereas in control animals the maximum cell lysis was obtained only on 16th day (25% cell lysis) Administration of terpenoids clearly enhanced the antibody dependent cell mediated cytotoxicity (ADCC) In tumor-bearing control animals maximum cell lysis was obtained only on the 16th day (20% cell lysis) But in the case of glycyrrhizic acid- and ursolic acid-treated groups, the maximum lysis was obtained on the 12th day and it was 47% and 325% cell lysis, respectively Intraperitoneal administr
TL;DR: The importance of using histopathological investigations to unravel the complex biological host/parasite interaction, which results in systemic lesions affecting reared marine species, is emphasized.
Abstract: Diseases caused by parasites are much more frequently described in cultured fish, which suffer from artificial conditions and numerous stress factors. This study investigates the histological, histochemical and morphometric modifications of splenic melanomacrophage centers (SMMCs) infected by Sparicotyle chrisophrii (Monogenea, ectoparasite of the gills) in sea breams (Sparus aurata), cultured in floating cages in the Gulf of Gaeta (Italy). Infected fish swam near the water surface, showing severe signs of anemia. Several spleens were collected from both healthy and dead fish (70-100 gr. body weight). A spleen histopathology was evaluated by using traditional stainings, such as Haematoxylin and Eosin (HE), Periodic Acid-Schiff reaction (PAS), Perl's reaction for haemosiderin and Schmorl's reaction for lipofuscins. Furthermore, SMMCs morphometry was performed on PAS-stained sections to study 7 morphometric parameters [Mean SMMCs profile area (MPA), Mean SMMCs maximum diameter (Media), Mean SMMCs minimum diameter (media), Mean SMMCs diameter (Dia), Mean SMMCs Perimeter (P), Mean SMMCs Form Factor (FF) and Mean SMMCs number per square millimeter of spleen tissue (MN)]. A light microscope of HE stained sections of spleen revealed a dramatic increase in the size and number of SMMCs in parasitized animals. Morphometric data illustrated statistically significant differences (p < 0.01) of all studied parameters between healthy and diseased fish. This study emphasizes the importance of using histopathological investigations to unravel the complex biological host/parasite interaction, which results in systemic lesions affecting reared marine species.
TL;DR: This study aims to determine serum levels of ROS in periparturient ewes, as well as to establish a value of reference of their physiological concentration to show a significant increase in ROS concentrations from the beginning to the end of the experiment.
Abstract: Reactive Oxygen Species (ROS) are produced during oxidative metabolism, and regulate many biological processes. The acute inflammation characterizing parturition induces many physiological changes. Among them, there is evidence that ROS affect the synthesis of many factors involved in parturition. Our study aims to determine serum levels of ROS in periparturient ewes, as well as to establish a value of reference of their physiological concentration. ROS determination was performed on blood collected every 12 hours in periparturient twin pregnant ewes. Our results will show a significant increase in ROS concentrations from the beginning to the end of the experiment. This increase may be due to the inflammatory process establishing during parturition.
TL;DR: EUK-189, a salen-manganese complex and superoxide dismutase/catalase mimetic, was administered subcutaneously (sc; 30 or 70 mg/kg) to mice at - 24, - 1, +1, or +6 h relative to whole-body cobalt-60 gamma irradiation (LD(90/30) dose), and survival was monitored for 30 days Cell counts and cytokines in circulation were measured in sublethally irradiated mice treated with EUK-189 EUK189 (70 mg/ kg,
Abstract: EUK-189, a salen-manganese complex and superoxide dismutase/catalase mimetic, was administered subcutaneously (sc; 30 or 70 mg/kg) to mice at - 24, - 1, +1, or +6 h relative to whole-body cobalt-60 gamma irradiation (LD(90/30) dose), and survival was monitored for 30 days Cell counts and cytokines in circulation were measured in sublethally irradiated mice treated with EUK-189 EUK-189 (70 mg/kg, - 24 h) enhanced 30-day survival with a dose reduction factor (DRF) of 115 (p = 0047, 95% confidence limits: 1053, 1244) LD(50/30)s were 796 and 913 Gy for saline- and EUK-189-treated groups, respectively Drug treatment was associated with elevations in numbers of total white blood cells, eosinophils, lymphocytes, and platelets in irradiated mice, compared to vehicle-injected, irradiated controls EUK-189 did not stimulate production of any cytokine or chemokine tested
TL;DR: The evidence presented in this study supports a hypothesis that C. sinensis activates macrophages by engaging Toll-like receptors and inducing mitogen-activated protein kinase (MAPK) pathways characteristic of inflammatory stimuli.
Abstract: Cordyceps sinensis is a fungus that has been used for over 2,000 years in China as a treatment for a variety of conditions including infectious diseases. The available evidence suggests a hypothesis that any efficacy of C. sinensis as an anti-infective therapeutic would be related to a role as an activator of innate immune responses. The objectives of this study were first to investigate the ability of C. sinensis to activate pro-inflammatory responses in macrophages in vitro and induce protective responses against intracellular pathogens in vivo, and second to characterize a method of action. We found that C. sinensis activates murine macrophages to produce a variety of pro-inflammatory cytokines. IFN-gamma synergizes with C. sinensis to amplify this response. Bacterial endotoxin contamination was ruled out as a potential artefact. The evidence presented in this study supports a hypothesis that C. sinensis activates macrophages by engaging Toll-like receptors and inducing mitogen-activated protein kinase (MAPK) pathways characteristic of inflammatory stimuli.
TL;DR: It is suggested that IFNbeta-1a effect in RRMS patients could be explained by its modifying effect on cytokine pattern, and a possible role of IL-10/ IL-12 ratio as a serum marker predictive of favorable clinical course is proposed.
Abstract: We examined the effects of interferon (IFN)beta-1a on interleukin (IL)-12p70 and IL-10 secretion in 27 Relapsing Remitting Multiple Sclerosis (RRMS) patients, divided in responders and non-responders. In responders, IFNbeta-1a does not change the IL-12p70 concentrations, but it leads to a remarkable increase in the IL-10 production. Besides, a high IL-10/IL-12 ratio is demonstrated during the first six months of therapy. In non-responders, there were not significant alterations in the cytokine profile. We suggest that IFNbeta-1a effect in RRMS patients could be explained by its modifying effect on cytokine pattern. Moreover, we propose a possible role of IL-10/ IL-12 ratio as a serum marker predictive of favorable clinical course.
TL;DR: Gamma irradiation effects on Cerastes cerastes venom showed that elicited antibodies to irradiated venoms were able to recognize native venom, and anti-2 kGy irradiated venom had more protective ability than anti-native venom, as tested in mice.
Abstract: Immunotherapy is the most effective treatment for the snake bites. The antivenoms are commonly obtained by hyperimmunization of animals that suffer from venom toxicity. The present report describes gamma irradiation effects on Cerastes cerastes venom. Doses of 1 kGy and 2 kGy gamma radiations were used for venom detoxification. These treated venoms did not have any residual lethal effects until 10 LD50. Immunological analysis of sera raised against native and irradiated venoms, showed that elicited antibodies to irradiated venoms were able to recognize native venom. Anti-2 kGy irradiated venom had more protective ability than anti-native venom, as tested in mice.
TL;DR: The aim of this study was to detect genes that code for superantigens in Streptococcus and Staphylococcus aureus isolates from psoriatic patients, and results might support the role of superantIGens in the exacerbation of psoriasis.
Abstract: Superantigens are powerful T lymphocyte-stimulating agents that are believed to contribute to the pathogenesis of certain diseases such as psoriasis. Toxins produced by Streptococcus pyogenes and Staphylococcus aureus are superantigens. The aim of this study was to detect genes that code for superantigens in Streptococcus and Staphylococcus aureus isolates from psoriatic patients. Primers to amplify streptococcal pyrogenic exotoxin A, B, and C and streptolysin O genes and staphylococcal enterotoxin A, B, C, and D genes were used. Streptococcal exotoxin B was detected in five streptococcal isolates. Staphyloccocus aureus enterotoxin A and/or C genes were detected in nine S. aureus isolates. Isolates from 13 of 22 patients possesed gene(s) that code for toxin(s) (superantigens). These results might support the role of superantigens in the exacerbation of psoriasis.
TL;DR: Raised serum TNF-α concentration, related to vascular endothelium damage as shown by increased vWf:Ag levels, occurred invariably in children affected by HSP both with and without renal involvement.
Abstract: In a longitudinal cohort study our aim was to evaluate the cytokine pattern of children affected by Henoch-Schonlein purpura (HSP) and to correlate this pattern to vascular endothelium damage and to nephropathy. The following parameters were monitored at the onset of the disease (T0) and after 6 months of follow-up (T1): clinical scores, serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), soluble IL-2 receptor (IL-2sRalpha), fibrinogen, von Willebrand factor antigen (vWf:Ag) and soluble thrombomodulin (TMD) levels. A total of 24 children (9 M, 15 F), affected by HSP, aged between 3-14 years (median 6 years), were enrolled into the study. IL-2 serum levels were significantly increased at the onset of the disease compared to control group and T1. The same pattern was observed for IL-2sRalpha and TNF-alpha. Fibrinogen and vWf:Ag concentrations were significantly higher at the onset of disease than t1 and in control group. TMD levels resulted constantly within the normal range. Concerning the analyzed parameters, no significant difference resulted to be in subjects with and without renal involvement (hematuria and/or proteinuria). Finally, raised serum TNF-alpha concentration, related to vascular endothelium damage as shown by increased vWf:Ag levels, occurred invariably in children affected by HSP both with and without renal involvement.
TL;DR: In vitro and in vivo evidence is accumulating that TNF-α is not the primary cytokine targeted by thalidomide in ENL and other inflammatory conditions.
Abstract: Thalidomide is used to treat erythema nodosum leprosum (ENL). The events that precipitate this inflammatory reaction, which may occur in multibacillary leprosy patients, and the mechanism by which thalidomide arrest ENL, are not known. Thalidomide's ability to inhibit tumor necrosis factor alpha (TNF-alpha) in vitro has been proposed as a partial explanation of its effective treatment of ENL. In in vitro assays, thalidomide can enhance or suppress TNF-alpha. This is dependent on the stimulant used to evoke TNF-alpha; the procedure used to isolate the mononuclear cells from blood, and the predominant mononuclear cell type in the culture. To avoid artifacts that may occur during isolation of mononuclear cells from blood, we stimulated normal human blood with LPS and evaluated the effect of thalidomide and dexamethasone on TNF-alpha, and other inflammatory cytokines and biomarkers. Thalidomide suppressed interleukin 1 beta (IL-1beta) (p = 0.007), and it enhanced TNF-alpha (p = 0.007) and interleukin 10 (IL-10) (p = 0.031). Dexamethasone enhanced IL-10 (p = 0.013) and suppressed IL-1beta, TNF-alpha, interleukin 6 (IL-6), and interleukin 8 (IL-8) (p = 0.013). The two drugs did not suppress: C-reactive protein (CRP), Ig-superfamily cell-adhesion molecule 1 (ICAM 1), tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor 2 (TNFR2), or amyloid A. In vitro and in vivo evidence is accumulating that TNF-alpha is not the primary cytokine targeted by thalidomide in ENL and other inflammatory conditions.
TL;DR: The immunomodulatory and immunorestorative properties of KV are established, which could be harnessed for possible clinical benefits to immunodeficient patients.
Abstract: The immunomodulatory properties of kolaviron (KV), a mixture of three related biflavonoids of Garcinia kola Heckel (Clusiaceae), were investigated. The study was conducted using in vitro and in vivo immunocompetent and immunocompromised animal models. KV (250 and 500 mg/kg) produced a dose-dependent and significant (p < 0.05) inhibition of delayed-type hypersensitivity in rats and also caused a significant (p < 0.05) increase in the primary and secondary sheep erythrocytes-specific antibody titres in rats. In vitro, KV inhibited the classical complement system at concentrations greater than 100 μg/ml. The administration of KV ameliorated the cyclophosphamide-induced leukopenia and increased the proportion of lymphocytes count in rats after 14 days of treatment. Administration of KV on alternate days after immunosuppression with cyclophospamide increased the rate of excision wound closure and reduced epithelialization period from 21.75 to 15.5 days. This study established the immunomodulatory and immunores...
TL;DR: Oral administration of Agaricus extracts ameliorates the Th1/Th2 balance from the Th2-skewed conditions and significantly decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in bronchial alveolar lavage fluids.
Abstract: We showed in a previous study that hot-water extracts of Agaricus blazei (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it remains unclear whether the Agaricus extracts ameliorate the skewed balance of type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice. When Meth A-bearing mice were given orally either Agaricus extracts or water once a day starting 5 days after tumor implantation, spleen T cells, prepared from tumor-bearing mice treated with Agaricus extracts, in response to anti-CD3 monoclonal antibody produced significantly higher levels of interferon γ (IFN-γ) than that of controls. The mRNA expression of IFN-γ-inducing protein 10 and the frequency of CD69+ or CD49d+ cells, among activated T cells infiltrated into tumors, significantly increased in Agaricus-treated mice, compared with those of tumor-controls. In asthma-induced mice, treatment with the Agaricus ex...
TL;DR: The inhibitory effect of the MeOH extract of Citri unshii pericarpium (CU) and its fractions were tested in hyperlipemic rats using for animal models induced by high cholesterol-diet as discussed by the authors.
Abstract: The inhibitory effect of the MeOH extract of Citri unshii pericarpium (CU) and its fractions were tested in hyperlipemic rats using for animal models induced by high cholesterol-diet. We measured plasma levels of triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol as measures of its hyperlipemic effects. We demonstrated that CU decreases plasma levels of triglyceride, total cholesterol and LDL cholesterol. There was also no elevation of plasma ALT and AST levels, which indicate CU did not cause liver injury. These results indicate that CU is a good candidate for the treatment on high cholesterol diet-induced blood circulatory disorders, obesity and hyperlipidemia.
TL;DR: In the blood biochemistry results, serum phosphorus, calcium, T3, and T4 remained unchanged, but blood estrogen levels were significantly increased in HER-S–treated rats, which suggests that estrogen is related to the mechanism of the HER–induced antiosteoporosis function in OVX rats.
Abstract: In this study, the authors have characterized the effect of HER-S (red ginseng, Angelicae gigantis Radix, Phyllostachys folium, and soybean extracts) on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in control, sham, OVX, OVX(beta-estradiol-treated), and OVX(HER-S-treated) rats. Light microscopic analyses showed a porous or eroded appearance on the femoral trabecular bone surface in OVX rats, whereas the femoral trabecular bone surfaces of the other groups (control, sham, OVX(17beta-estradiol-treated), and OVX(HER-S-treated) rats) were composed of fine particles. The femoral trabecular bone area and number were decreased in OVX rats, but these reductions were significantly prevented by the administration of HER-S for 7 weeks, similar to estrogen. In the blood biochemistry results, serum phosphorus, calcium, T(3), and T(4) remained unchanged, but blood estrogen levels were significantly increased in HER-S-treated rats, which suggests that estrogen is related to the mechanism of the HER-S-induced antiosteoporosis function in OVX rats.
TL;DR: It is suggested that HO-1 plays an important role in CHS and is an important pharmacological target for the treatment of CHS.
Abstract: Heme oxygenase (HO)-1 may have an important role in the resolution of T cell–mediated inflammation. The authors elucidated the role of the anti-inflammatory HO-1 in the pathogenesis of skin inflammation, using a mouse contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB). Ear swelling was induced by challenge with DNFB, accompanied by infiltration of inflammatory cells in the challenged ear skin. DNFB challenge induced low levels of HO-1 mRNA and protein expression. Ear swelling induced by DNFB challenge was significantly reduced by topical treatment with cobalt protoporphyrin IX (CoPP), a HO-1 inducer, but exaggerated by blockage of HO-1 activity with tin protoporphyrin IX (SnPP), a HO-1 inhibitor. Similarly, the number of infiltrated cells in DNFB-challenged ear skin were reduced by CoPP but increased by SnPP. Our findings suggest that HO-1 plays an important role in CHS and is an important pharmacological target for the treatment of CHS.
TL;DR: To generate vaccine candidates with antigen and adjuvant properties in one molecule the authors have chemically introduced zwitterionic motifs into naturally anionic PS and find that the resulting ZPS are TLR2 agonists, able to activate human and mouse APCs.
Abstract: Bacterial capsular polysaccharides (PS) which naturally contain zwitterionic charge motifs (ZPS) possess specific immunostimulatory activity, leading to direct activation of antigen-presenting cells (APCs) through Toll-like receptor 2 (TLR2) and of T cells in co-culture systems. When administered intraperitoneally, ZPS and bacteria expressing them are involved in the induction or regulation of T-cell dependent inflammatory processes such as intra-abdominal abscess formation. To generate vaccine candidates with antigen and adjuvant properties in one molecule we have chemically introduced zwitterionic motifs into naturally anionic PS and find that the resulting ZPS are TLR2 agonists, able to activate human and mouse APCs. Since T-regulatory cells and other T-cell subsets express TLR2, and TLR2 engagement modifies functionality and activation state of these cells, we speculate that most effects induced by natural and chemically derived ZPS may be explained by their TLR2 agonist properties, presumably through...
TL;DR: Prevalence of legume allergy and concomitant sensitization to different allergens was evaluated in patients of asthma and/ or rhinitis and only six patients showed prick test positivity compatible with their anamnesis.
Abstract: Prevalence of legume allergy and concomitant sensitization to different allergens was evaluated in patients of asthma and/ or rhinitis. Skin prick test with 27 common food allergens and 61 aeroallergens in 76 subjects was performed. Out of 76 subjects, 41 perceived allergenic problems with different food items as contributing factor. Only six patients showed prick test positivity compatible with their anamnesis. However, 35 subjects showed sensitization to different food items, out of which thirty were sensitive to legumes. The common foods in decreasing order of allergenicity were chickpea, followed by green gram, egg white, and bean fresh/red gram. Concomitant sensitization to different legume crops was found in patients.
TL;DR: M. vaccae to OVA-sensitized pregnant BALB/c mice prevented Th2 immune responses by enhancing secretion of IFN-γ and lowering IL-5 levels during pregnancy and the effect persisted during the postnatal period in offspring.
Abstract: Although the development of atopy in the newborn is determined by a multitude of factors, an intense Th1 stimulus early in life could be protective by facilitating a switch away from Th2. Aimed to determine the effect of single Mycobacterium vaccae (M. vaccae) immunization to OVA-sensitized pregnant mice on IL-5 and IFN-gamma secretion from placental lymphocytes and splenocytes of offspring. Pregnant BALB/c mice were divided into 4 groups, OVA-sensitized + M. vaccae immunized, OVA-sensitized, M. vaccae immunized and controls. Sensitization with OVA was initiated before mating, and aerosol OVA challenge were performed during pregnancy. M. vaccae immunization was performed on the 12(th) day of pregnancy. IL-5 and IFN-gamma levels of placental lymphocytes were analyzed on the 18(th) day of pregnancy and splenocytes of offspring on the 2(nd) and 28(th) days during postnatal period. A single administration of M. vaccae to OVA-sensitized pregnant mice downregulated IL-5 secretion and induced IFN-gamma secretion from placental lymphocytes. On the other hand, after M. vaccae immunization downregulation of IL-5 levels and upregulation of IFN-gamma secretion persisted in offspring when determined on 2(nd) and 28(th) days of life. Vaccination with M. Vaccae to OVA-sensitized pregnant BALB/c mice prevented Th2 immune responses by enhancing secretion of IFN-gamma and lowering IL-5 levels during pregnancy and the effect persisted during the postnatal period in offspring.
TL;DR: It is confirmed that a more aggressive biologic behavior of canine MCT is associated with the increased c-Kit expression, further suggesting a new role for c-kit, as a useful marker, in diagnostic pathology and in tumor progression.
Abstract: Canine cutaneous mast cell tumor (MCT) is very common disease in dogs, this is more aggressive than in other species. The biologic behavior of MCT is highly variable and a more accurate prognosis for these tumors needs to performed. The proto-oncogene c-kit is known to play a critical role in development and function of mast cells (MC).The aim of this study was to evaluate the expression of immunohistochemical pattern of c-kit in MCTs and to correlate these results with MC density (MCD) and intratumoral microvessel density (MVD). Our results confirm that a more aggressive biologic behavior of canine MCT is associated with the increased c-kit expression, further suggesting a new role for c-kit, as a useful marker, in diagnostic pathology and in tumor progression.
TL;DR: The reduction of IL-5, involved in the late regulation of B cell differentiation into Ig-secreting plasma cells, may contribute to the defective antibody production in CVI patients.
Abstract: We evaluated the capacity of peripheral CD4+ T helper cells in four Common Variable Immunodeficiency (CVI) patients to secrete interleukin-4 (IL-4) and IL-5.While in control CD4+ T cells, stimulated via CD3 and cultured in presence of IL-2 or IL-15, a 10 fold increased production of IL-5 (146 ± 30; 142 ± 25 pg/ml) was found, a 4 fold increment of this cytokine was, instead, detected in 3 out of 4 CVI patients (34 ± 13; 39 ± 12 pg/ml) (p < 0.05). In conclusion, the reduction of IL-5, involved in the late regulation of B cell differentiation into Ig-secreting plasma cells, may contribute to the defective antibody production in CVI patients.