Showing papers in "Immunopharmacology and Immunotoxicology in 2015"
TL;DR: Comparisons of the ameliorative effect of Spirulina and Dunaliella in experimental colitis showed that in comparison to Sulfasalazine, SP exhibited better therapeutic and safety profile than DS against acetic acid-induced UC.
Abstract: Context: Spirulina platensis (SP) is used as a source of protein and vitamin supplement in humans without any significant side-effects. Dunaliella salina (DS) is also regarded as one of the richest natural producers of carotenoid, thus used as a source of antioxidants to protect cells from oxidative damage.Objective: The aim of the present study is to compare the ameliorative effect of Spirulina and Dunaliella in experimental colitis.Materials and methods: Spirulina and Dunaliella were investigated at the same dose of 500 mg/kg body weight for their modulatory effect against acetic-acid induced ulcerative colitis (UC) in rats. The colonic lesion was analyzed by examining macroscopic damage, bloody diarrhea scores, colon weight/length and change in body weight of tested rats. Colon lipid peroxidation and oxidative stress markers were examined by evaluating malondialdehyde (MDA), protein carbonyl (PCO), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD). Colon inflammatory mark...
125 citations
TL;DR: A short review of the advancements in adjuvant technology, current clinical scenario of new adjuvants and application of their molecularly defined formulations to new generation cancer vaccines which are currently under development.
Abstract: Despite recent breakthroughs in the prognosis, prevention and treatment, cancer still remains the leading cause of death and affects millions of people worldwide. With the US FDA approval of various preventive cancer vaccines such as Gardasil (Merck), Cervarix (Glaxosmithkline) and the therapeutic vaccine Sipulencel-T (Provenge), cancer vaccine development is gaining huge ground. Approval of these vaccines has encouraged the concept of cancer treatment through cellular immunotherapy. The FDA approval of the above vaccines has provided support for renewed interest and attention which the development of new therapeutic cancer vaccines deserves. However, most of the new generation vaccines including that for cancer are poorly immunogenic sub-unit vaccines and thus essentially need adjuvants in their formulations to compensate for the immune suppression. Adjuvants are the essential components of a potent vaccine which increases the efficacy by enhancing the antigen-specific immune response. However, the design of a successful adjuvant is not easy because of the complexity and the difficulty in designing adjuvants that are safe, potent and economically viable. The present communication takes a short review of the advancements in adjuvant technology, current clinical scenario of new adjuvants and application of their molecularly defined formulations to new generation cancer vaccines which are currently under development.
85 citations
TL;DR: It is concluded that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI.
Abstract: We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves...
73 citations
TL;DR: The results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals, and shows no significant difference in hematological, biochemical, and histopathological parameters in rats.
Abstract: Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecuti...
49 citations
TL;DR: Findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.
Abstract: Cinobufagin (CBG) is a cardiotoxic bufanolide steroid secreted by the skin and parotid venom glands of the Asiatic toad Bufo bufo gargarizans (called Chan-Su). Although CBG is known to exhibit anti-cancer activities, very little is known about its potential mechanism(s) of action. In this study, we investigated whether CBG mediates its effect through the modulation of the mitogen-activated protein kinases (MAPKs) signaling pathway in human multiple myeloma (MM) U266 cells. We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells. CBG showed much higher cytotoxicity against U266 cells as compared to peripheral blood mononuclear cells (PBMC). Induction of CBG increased reactive oxygen species (ROS) generation from mitochondria, which is associated with the induction of apoptosis as characterized by increased sub-G1 DNA contents of cell cycle, positive Annexin V binding, activation of caspase-3 and cleavage of PARP. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis. CBG also down-regulated the expression of various downstream gene products that mediate cell proliferation, survival, angiogenesis and metastasis. Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells. Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.
43 citations
TL;DR: The finding suggested that the combination of CGA and Lut may be a potential therapeutic treatment for the inflammatory proliferation of synoviocytes in patients with RA.
Abstract: Context: Chlorogenic acid (CGA) and luteolin (Lut) are the predominant constituents of Caulis Lonicerae, which is usually used in the treatment for rheumatoid arthritis (RA).Objective: In this study, we investigated whether CGA and Lut could synergistically inhibit the proliferation of fibroblast-like synoviocytes (FLSs) in RA synovial tissues.Methods: Rat FLS cells (RSC-364) induced by interleukin (IL)-1β were treated by CGA, Lut or both of them. The apoptosis rates were detected by flow cytometer. Protein expression of key molecules of NF-κB and JAK/STAT signaling pathways were detected by Western blot.Results and discussion: Treatment with CGA and Lut inhibited the proliferation of RSC-364 cells stimulated by IL-1β significantly and induced cell apoptosis notably. The ratio of apoptosis in RSC-364 cells induced with IL-1β accompanied by both CGA and Lut increased approximately 7-fold compared with those incubated with IL-1β alone. The results of immunoblot analysis revealed that the key molecul...
42 citations
TL;DR: ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-кB and activating PI3K/AKT signaling pathway.
Abstract: Context: Astragaloside IV (ASI) is a major and active saponin derivative of Astragalus membranaceus (Fisch) Bge. The anti-inflammatory properties of ASI are important for its cardioprotective effects. However, the molecular mechanisms of the protective effect of ASI on lipopolysaccharide (LPS)-induced cardiac dysfunction is yet to be elucidated.Objective: This study was designed to investigate the therapeutic effects and possible mechanisms of ASI against LPS-induced septic cardiac dysfunction and inflammation in mice.Materials and methods: Mice were intraperitoneally injected with ASI (20 mg/kg) for 1 week before LPS challenge (10 mg/kg, i.p.). Left ventricular performance and morphology were analyzed using echocardiography 6 h after LPS induction. Activities of lactate dehydrogenase (LDH) in serum were measured and serum levels of cardiac troponin I (cTnI) were quantified by ELISA. Serum levels of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and I...
40 citations
TL;DR: It is shown that norepinephrine (NE) enhanced the expansion of human MDSCs in vitro, providing important insights into the novel roles of neurotransmitters in the regulation of myeloid cell differentiation and function.
Abstract: Increased numbers of myeloid-derived suppressor cells (MDSCs) are often observed in various pathological and physiological conditions. However, the interactions between neurotransmitters and MDSCs have not been elucidated. In this study, we studied whether norepinephrine (NE), a neurotransmitter, could affect the differentiation of human MDSCs in vitro. Flow cytometric analysis showed that treatment with 20 μM NE significantly enhanced the expansion of MDSCs. The NE-generated MDSCs suppressed the T-cells proliferation, depending on the production of reactive oxygen species (ROS). Moreover, the expansion of MDSCs induced by NE resulted in a dramatic induction of nicotinamide adenine dinucleotide phosphate oxidase subunit P47phox. Addition of the ROS inhibitor catalase into the MDSCs/T-cell co-culture system partly abrogated the suppressive effects of MDSCs on T-cell proliferation. In summary, our data have shown that NE enhanced the expansion of human MDSCs in vitro, providing important insights in...
38 citations
TL;DR: In vivo experiments showed that imperatorin reduced TPA-induced ear thickness/weight, cutaneous cytokines expression and improved histopathological features as well as inhibition of the pro-inflammatory cytokines production in LPS-stimulated mice.
Abstract: Context: Foeniculum vulgare (F. vulgare) is traditionally used to treat inflammatory diseases. Recently, anti-inflammatory and antioxidant activities of methanol extract of the fruits of F. vulgare were reported. To identify biologically active compounds responsible for the anti-inflammatory activity, we isolated four coumarins, scopoletin, 8-methoxypsoralen, bergapten and imperatorin from the fruits of F. vulgare.Objective: This study assessed the anti-inflammatory and antioxidant effects of coumarins isolated from F. vulgare in lipopolysaccharide (LPS)-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice.Materials and methods: RAW 264.7 cells were treated with the coumarins (30 µM) and then stimulated with LPS (100 ng/ml). Ears of ICR mice were treated with TPA (1 µg/ear) once a day. Ten microliters each of the four coumarins (200 μg/ml) were topically applied to the ears for 3 days. Antioxidant activities were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) ...
34 citations
TL;DR: It is clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.
Abstract: IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague-Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200 μg/kg/d intragastrically) from 12 to 28 weeks. At Week 28, the rats was sacrificed, kidneys and blood samples were collected for further analysis. Our data shown that IgAN rat model showed marked deterioration of proteinuria together with higher levels of the urine protein:creatinine ratio compared to the normal control. Animals that underwent intermittent exposure to triptolide treatment exhibited significant improvements in the functional parameters without severe side effects. Rats developing IgAN had profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, while triptolide treatment significantly attenuated it. We also observed that treatment with triptolide significantly decreases serum levels of IL-1β and IL-18, and may exerted anti-inflammatory effects by down-regulating NLRP3 and TLR4 expression. Our study clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.
34 citations
TL;DR: It is demonstrated that the suppression of crocin on airway inflammation and hyper-reactivity in a murine model, thus crocin might have a great potential to be a candidate for the treatment of asthma.
Abstract: Context: Crocin, a diterpenoid glucoside, has multitudinous activities such as anti-inflammation, anti-allergy, anti-oxidation and relaxing smooth muscles.Objective: In this study, the potential of crocin as an anti-asthma agent was investigated in a murine model.Materials and methods: BALB/c mice were sensitized and challenged by ovalbumin (OVA) to induce allergic airway inflammation, with crocin administered one hour before every OVA challenge. Airway hyper-reactivity was evaluated by lung function analysis systems. Leukocyte counts in bronchoalveolar lavage fluid (BALF) were measured by a hemocytometer and Diff-Quick-stained smears. Lung tissues were stained with hematoxylin–eosin, Congo red and methylene blue for histopathological inspection. Inflammatory mediators in serum, BALF and lung were measured by ELISA or RT-PCR. Effects of crocin on MAPK signaling pathways were investigated by western blot analysis.Results: Crocin significantly suppressed airway inflammation and hyper-reactivity, red...
TL;DR: Administration of either CoQ10 or amlodipine was found to protect against acetic acid-induced colitis, and their combination was more effective than individual administration of either of them.
Abstract: Context: Ulcerative colitis is a chronic inflammatory bowel disease. Recent studies reported a pivotal role of elevated intracellular calcium in this disorder. Coenzyme Q10 (CoQ10) and amlodipine are known to maintain cellular energy, decrease intracellular calcium concentration in addition to their antioxidant and anti-inflammatory properties.Objective: The aim of this study was to evaluate the possible protective effects of CoQ10, amlodipine and their combination on ulcerative colitis.Materials and methods: Colitis was induced in rats by intracolonic injection of 3% acetic acid. CoQ10 (10 mg/kg), amlodipine (3 mg/kg) and their combination were administered for 8 consecutive days before induction of colitis.Results: Our results showed that administration of CoQ10, amlodipine and their combination decreased colon tissue malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE2), myeloperoxidase (MPO) and heat shock protein (HSP70) levels induced by intr...
TL;DR: The study shows that Lutein protects against skeletal IR injury by down regulating oxidative stress and inflammatory mechanisms.
Abstract: Background: Lutein is an antioxidant compound with potential biological effects. The present study investigated the protective role of Lutein against I/R injury in skeletal muscle.Methods: Animals were divided into three groups. Group I – sham operated; Group II- IR injury- Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h of ischemia, the clamp was removed and the animals underwent 2 h of reperfusion. Group III-Lutein + IR injury- Rats with Lutein treatment received intraperitoneal injection 1 h before reperfusion. The skeletal tissues were analyzed for oxidative stress parameters (reactive oxygen species, protein carbonylation and sulfhydryls, lipid peroxidation). Antioxidant status was determined by evaluating Nrf-2 levels and antioxidant enzyme activities. The inflammatory mechanism was determined through NF-κB and COX-2 expressions. Pro-inflammatory cytokines were determined by ELISA.Results: The results showed that Lutein treatment significantly decreas...
TL;DR: An overview of literature with regard to Li's effects on different immune cells is provided based on the existing studies to understand the mechanistic basis and heterogeneous responses of Li's effect in bipolar, also unravel relative immune disorders.
Abstract: One of the remarkable discoveries in the field of psychopharmacology from late 1940s is Lithium (Li) that reminds of old but still gold. It continues to be a distinctive mood stabilizer that matches various standards recommended for mood stabilizers. Apart from this Li is also known to affect immune cell functions. Lithium response and regulations of different immune cells in bipolar patients, related immune disorders are not well defined. Here, we provide an overview of literature with regard to Li's effects on different immune cells. However, the use of Li is currently limited to bipolar disorders and there is no empirical evidence for immune cell disorders. The objective of this article is to provide the evaluations of Li responses towards the different immune cells based on the existing studies. Further, more studies are needed to understand the mechanistic basis and heterogeneous responses of Li's effect in bipolar, also unravel relative immune disorders.
TL;DR: The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-β and Foxp3 gene expressions and an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE.
Abstract: Context: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention.Objective: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model.Materials and methods: Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund’s adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks ...
TL;DR: SA significantly, although variably, augments the cytotoxicity of saporin and saporine-based immunotoxins and potentially improves the therapeutic window of targeted toxins.
Abstract: Context: Saponinum album (SA) is a complex mixture of triterpenoid saponins previously shown to augment the cytotoxicity of the type I ribosome-inactivating protein saporin and an EGF-saporin target toxin that could potentially be used to improve the therapeutic window of targeted toxins.Objective: To investigate the augmentative property of SA on saporin and saporin-based immunotoxins (IT) directed against five different cell surface target molecules on human leukemia and lymphoma cells.Materials and methods: After determining the optimum dose of SA for each cell line, the extent of SA-mediated augmentation was established for saporin and five saporin-based ITs using XTT and an annexin V apoptosis assay. Immunospecificity was investigated using three different blocking assays. Dose-scheduling was also investigated using the XTT assay.Results: Uncorrected SA-mediated augmentation ranged at best from 31.5 million-fold to, at worse, 174-fold. However, when the calculated fold-increases were adjusted...
TL;DR: The results suggested that osthole could promote the activation of the tumor-infiltrating CD4+ T and CD8+ T cells, and elevate the proportion of CD4- andCD8+ effector T cells in tumor tissues and in the spleen.
Abstract: Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC.
TL;DR: Data indicate that CuB possesses immunomodulatory and anti-inflammatory effects, and it may be used as an effective herbal remedy for the treatment and prevention of inflammation.
Abstract: Cucurbitacin B (CuB) is a triterpenoid that is widely distributed in the plant kingdom and has a variety of biological activities. However, the immunomodulatory and anti-inflammatory effects of CuB have not been well characterized. Therefore, in this study, we investigated the effects of CuB on parameters related to antigen presentation and T-cell activation. Specifically, we examined the effects of CuB on basal and lipopolysaccharide (LPS)-induced expression of class I and II MHC molecules, CD40, CD54, CD80, and CD86 in peritoneal macrophages. The LPS-a expression of MHC II, CD40, CD54, and CD80 was significantly attenuated by CuB. However, expression levels of MHC I and CD86 were not changed by CuB. CuB inhibited the production of intracellular reactive oxygen species induced by LPS and blocked the LPS-activated release of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-6, IL-12, and IL-1β, without any cytotoxicity. Consistent with this, CuB also reduced the expression levels of inducible NO synthase and cyclooxygenase-2 induced by LPS. Furthermore, we demonstrated that the anti-inflammatory effects of CuB were dependent on the induction of heme oxygenase-1 expression via Nrf2 activation. Taken together, these data indicate that CuB possesses immunomodulatory and anti-inflammatory effects, and it may be used as an effective herbal remedy for the treatment and prevention of inflammation.
TL;DR: It is suggested that HDN or garlic oil, the natural antioxidants, can alleviate DZN induced hemato- and immunotoxicity.
Abstract: Diazinon (DZN) has been used for several years in agriculture and urban applications leading to a variety of negative effects on health. Hesperidin (HDN) and garlic oil are naturally occurring compounds present in fruits and vegetables, which have been reported to have antioxidants and anti-inflammatory actions. This study was undertaken to throw light on the modulatory effect of HDN or garlic oil against hemato- and immunotoxicity induced by DZN in Wistar rats. Oral administration of DZN for 30 days resulted in significant decrease in RBCs count, Hb content, Ht value, platelet count, and relative lymphocyte and monocyte counts when compared with control groups. Moreover, DZN reduced significantly the serum total immunoglobulin concentration, hemagglutination titer, quantitative hemolysis of SRBCs, delayed type hypersensitivity, blood mononuclear cell proliferation, phagocytic index and blood T-cell subtypes (CD4(+) and CD8(+)) in comparison with vehicle treatment. Co-administration of HDN or garlic oil, 30 min before DZN was able to normalize most of the hematological and immunological parameters. These results suggested that HDN or garlic oil, the natural antioxidants, can alleviate DZN induced hemato- and immunotoxicity.
TL;DR: Results identified ursolic acid as a major anti-inflammatory compound in guava leaves.
Abstract: Psidium guajava (guava) leaves have been frequently used for the treatment of rheumatism, fever, arthritis and other inflammatory conditions. The purpose of this study was to identify major anti-inflammatory compounds from guava leaf extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n-butanol- and water-soluble phases derived from guava leaves were evaluated to determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO production in a dose-dependent manner without cytotoxicity at a concentration range of 0–100 μg/mL. The n-butanol soluble phase was the most potent among the five soluble phases. Four compounds were isolated by reversed-phase HPLC from the n-butanol soluble phase and identified to be avicularin, guaijaverin, leucocyanidin and ursolic acid by their NMR spectra. Among these compounds, ursolic acid inhibited LPS-induced NO production in a dose-dependent ...
TL;DR: Phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy and elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth.
Abstract: To date, several small molecule inhibitors and monoclonal-antibodies (like ICR-62) have been used to treat tumors over-expressing epidermal growth factor receptor (EGFR). However, the limitations associated with these conventional applications accentuate the necessity of alternative approaches. Mimotopes as compelling molecular tools could rationally be employed to circumvent these drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide mimotope is exploited as a vaccine candidate. It exhibited high affinity towards ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization, phage-based mimotope vaccine induced humoral immunity. Elicited anti-EGFR mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine was tested on the Lewis lung carcinoma mice model to investigate the prophylactic and therapeutic effects. The tumor volume was measured and recorded in different animal groups to evaluate the anti-tumor effects of the vaccine. Our data indicate that the reported phage-based mimotope could potentially elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth. However, in vivo experiments of prophylactic or therapeutic vaccination showed no specific advantage. Furthermore, phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy.
TL;DR: A significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-β or LPS/IFN-γ/IFn-β is found and a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells.
Abstract: Astrocytes actively play a pivotal role in inflammatory disease intensity of central nervous system especially multiple sclerosis (MS). Although IFN-β is a selective therapy for MS but the role of IFN-β in stimulating the astrocytes to produce cytokines is not clearly revealed. Therefore, it is encouraging to assess the modulatory role of IFN-β on astrocytes of brain tissue. The aim of our study was to analyze the molecular mechanisms of recombinant IFN-β 1a directly affecting IL-10, iNOS, MMP-9 and TIMP-1 expression in central nervous system for the first time. In this way, in vitro procedures conducted by human astrocytoma A172 and 1321N1 cell lines as a model system. The total RNA from A172 and 1321N1 cells treated with IFN-β and LPS/IFN-γ/IFN-β and untreated cells were extracted and evaluated for IL-10, iNOS, MMP-9 and TIMP-1 expression by real-time RT-PCR. We found a significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-β or LPS/IFN-γ/IFN-β. Moreover, a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells. Eventually there were no significant changes concerning the modulation of the MMP-9 and TIMP-1 in response to IFN-β treatment. In part, the immunomodulatory effect of IFN-β may be due to increase of IL-10 and suppression of iNOS expression in astrocytes of brain tissue.
TL;DR: The results suggest that 6-OHDA administration in mice can a potential tool for understanding mechanisms underlying adaptive immune activation-induced neurodegeneration in Parkinson’s disease.
Abstract: Context: Neuroimmunological response is associated with neurodegeneration in the human substantia nigra (SN) in Parkinson’s disease (PD).Objective: To explore the possibility that the neurotoxin, 6-hydroxydopamine (6-OHDA), could be used as a tool in mice to understand the immune response in PD.Materials and methods: We employed unilateral administration of 6-OHDA into the mouse SN. At 1 week, 2 weeks and 4 weeks post-injection, we used immunohistochemistry for the markers Iba-1 and gp91PHOX to investigate activated microglia in the SN. To examine the adaptive immune response, we used immunohistochemistry for CD3-positive T-lymphocytes, CD45R-positive B-lymphocytes and anti-mouse immunoglobulin-G (IgG). Dopamine neuron loss was examined using immunohistochemistry for the dopamine neuron marker, tyrosine hydroxylase.Results: Compared to vehicle, 6-OHDA administration induced an intense IgG deposition in the SN as well as increased infiltration of both T- and B- lymphocytes into the injected side of...
TL;DR: The data demonstrated that the dosage of 0.6 mg/kg AFB1 in broiler diet reduced the number of IgA+ cell and the expression of Ig a, pIgR, IgM and IgG mRNA in the small intestine.
Abstract: Aflatoxin B1 (AFB1) is the most toxic group of mycotoxins produced by two species of the Aspergillus, common contaminants of food and animal feed. The purpose of our study was to determine the effect of AFB1 on the number of IgA+ cell and immunoglobulin mRNA expression in the intestine of broilers. One hundred and fifty six one-day-old healthy Cobb broilers were randomly divided into the control group (the dosage of 0 mg/kg AFB1) and AFB1 group (the dosage of 0.6 mg/kg AFB1) with three replicates per group and 26 birds per replicate for 21 days, respectively. After necropsy at 7, 14 and 21 days of age, duodenum, jejunum and ileum samples were taken for analyzing IgA+ cell by immunohistochemistry and IgA, pIgR, IgM and IgG mRNA expression by qRT-PCR. IgA+ cells were mainly distributed in the lamina propria of small intestinal mucosa in both groups at 14 and 21 days of age. A significant decrease in the number of IgA+ cells in the duodenum, jejunum and ileum was revealed in the AFB1 group compared w...
TL;DR: Treatment with this algal omega-3 fatty acid concentrate resulted in significant down-regulation of LPS-induced production of TNF-α and IL-6 by peripheral blood mononuclear cells (PBMCs).
Abstract: The health benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA), mainly eicosapentaenoic acid (EPA 20:5) and docosahexaenoic acid (DHA, 22:6), have been long known. Although various studies have demonstrated the health benefits of ω-3 PUFA, the mechanisms of action of ω-3 PUFAs are still not completely understood. While the major commercial source is marine fish oil, in this study we suggest the marine micro algae, Dunaliella salina as an alternate source of omega-3 fatty acids. Treatment with this algal omega-3 fatty acid concentrate (Ds-ω-3 FA) resulted in significant down-regulation of LPS-induced production of TNF-α and IL-6 by peripheral blood mononuclear cells (PBMCs). The concentrate was also found to be a potent blocker of cyclooxygenase (COX-2) and matrix metalloproteinase (MMP-2 and MMP-9) expression. The present study reveals the anti-inflammatory properties of Ds-ω-3 FA concentrate including the inhibition of NF-κB translocation.
TL;DR: It is demonstrated that dasatinib had beneficial effects on EAE by lower incidence, attenuation in the severity and a delay in the onset of disease.
Abstract: Background: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS.Methods: We performed EAE induction in female C57BL/6 mice by myelin oligodendrocyte glycoprotein35–55 (MOG35–55) in Complete Freund’s Adjuvant (CFA) emulsion, and used dasatinib for the treatment of EAE. During the course of study, clinical evaluation was assessed, and on day 21 post-immunization blood samples were taken from the heart of mice for tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and antioxidants capacity evaluation. The mice were sacrificed and brains and cerebellums of...
TL;DR: It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways.
Abstract: Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component of Abeliophyllum distichum (White Forsythia) which is a deciduous shrub native to the south and central areas of Korea. The present study is designed to evaluate the anti-inflammatory activities and underlying mechanisms of isoacteoside in human mast cell line, HMC-1 cells. We isolated isoacteoside from A. distichum. The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) secretion and mRNA expression by ELISA and RT-PCR, respectively. In addition, mechanism related to anti-inflammatory was investigated by Western blotting. Isoacteoside significantly suppressed the production and mRNA expression of proinflammatory cytokines including IL-1β, IL-6, IL-8 and TNF-α in PMACI-stimulated HMC-1 cells without cytotoxicity. It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways. Taken together, the present findings provide new insights that isoacteoside may be a promising anti-inflammatory agent for inflammatory disorders.
TL;DR: Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis and exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.
Abstract: Context: Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects.Objective: This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway.Materials and methods: Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson’s trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproli...
TL;DR: The analysis of data over a 30-year period confirmed that SCIT with inhalant allergens conducted strictly according to the standard protocols and when administrated by experienced staff is a safe method of treatment with only a few side-effects.
Abstract: Context: Although subcutaneous allergen immunotherapy (SCIT) is effective in allergic rhinitis (AR) and asthma, it carries a risk of local and systemic adverse reactions.Objective: The aim of this study was to evaluate the rates and clinical characteristics of local and systemic reactions (LR and SR), and to identify their relation of demographic features, allergen extracts and diagnosis.Materials and methods: This study analyzed the administration of SCIT from 1983 to 2013; involving 1816 patients affected by allergic asthma and/or AR.Results: The rates of SR from SCIT were 0.078% per injection and 9% per patient. According to the World Allergy Organization 2010 grading system, 91 grade 1 reactions (44%), 67 grade 2 reactions (32.3%), 33 grade 3 reactions (16%) and 16 grade 4 reactions (7.7%) were seen. There was no fatal outcome from any of the SRs. Risk factors for a SR included: aluminium-adsorbed extract, pollen-containing vaccines, large LR and recurrent (≥2) LRs. The total LR rates were 0.0...
TL;DR: The data from these studies suggested to us that these six alkaloids might effectively reduce inflammatory responses in situ via changes in the formation of these key regulatory molecules/proteins.
Abstract: The aim of this study was to investigate the anti-endotoxin effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine and evodiamine alkaloids commonly found in Chinese herbal medicines. Porcine endothelial cells were challenged with 1 μg LPS/ml for 3 h and then treated with one of the six alkaloids at three concentrations (1, 5 or 10 μg/ml) for a further 21 h. The supernatants of the cultures were then collected and analyzed for levels of nitric oxide (NO), interleukin (IL)-10, intercellular cell adhesion molecule-1 (ICAM-1) and IL-2 using ELISA kits. The results revealed that sinomenine, stachydrine and chuanxionggzine inhibited production of NO; stachydrine and evodiamine inhibited secretion of IL-10; sinomenine and chuanxionggzine down-regulated ICAM-1 expression; oxymartrine and evodiamine decreased production of IL-2 by the LPS-stimulated endothelial cells. Overall, the data from these studies suggested to us that these six alkaloids might effectively reduce inflammator...