Showing papers in "Immunopharmacology and Immunotoxicology in 2012"
TL;DR: Results are provided, providing the first evidence that PI3K dependent signaling is involved in the inflammatory responses of microglial cells following LPS stimulation, may be useful in preventing inflammatory based neurodegenerative processes.
Abstract: Upregulation of inflammatory responses in the brain is associated with a number of neurodegenerative diseases. Microglia are activated in neurodegenerative diseases, producing pro-inflammatory mediators. Critically, lipopolysaccharide (LPS)-induced microglial activation causes dopaminergic neurodegeneration in vitro and in vivo. The signaling mechanisms triggered by LPS to stimulate the release of pro-inflammatory mediators in microglial cells are still incompletely understood. To further explore the mechanisms of LPS-mediated inflammatory response of microglial cells, we studied the role of phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathways known to be activated by toll-like receptor-4 signaling through LPS. In the current study, we report that the activation profile of LPS-induced pAkt activation preceded those of LPS-induced NF-κB activation, suggesting a role for PI3K/Akt in the pathway activation of NF-κB-dependent inflammatory responses of activated microglia. These results, providing the first evidence that PI3K dependent signaling is involved in the inflammatory responses of microglial cells following LPS stimulation, may be useful in preventing inflammatory based neurodegenerative processes.
91 citations
TL;DR: An overview of pro- and anti-inflammatory cytokine activity in AD is provided and their effects in disease progression and neurodegeneration remain an area of investigation.
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by destructive alterations of neurons (neurofibrillary tangles and amyloid plaques), and cognitive impairment. Inflammation is a key pathological hallmark of AD, thus the clinical and immunopathological evidence could be supported by potential role of inflammatory cytokines in AD, which may actively contribute to disease progression and chronicity. However, their effects in disease progression and neurodegeneration remain an area of investigation. This review article provides an overview of pro- and anti-inflammatory cytokine activity in AD.
61 citations
TL;DR: It is proposed that the immunostimulatory properties of individual honeys relate to their particular content of LPS, apalbumins, the 5.8 kDa component and AGPs, which are particularly dependent on AGPs derived from the nectar of kanuka flowers.
Abstract: Context: Factors in honey that improve wound healing are poorly understood, but are thought to include lipopolysaccharide (LPS), apalbumin-1 and -2, and a 5.8 kDa component that stimulate cytokine release from macrophages.Objective: To characterize the ability of New Zealand honeys to elicit the release of tumor necrosis factor-α (TNF-α) from monocytic cell lines as a model for early events within a wound site.Materials and methods: The ability of kanuka (Kunzea ericoides), manuka (Leptospermum scoparium), and clover (Trifolium spp.) honeys to stimulate the release of TNF-α from monocytic cell lines THP-1 and U937 was assayed by ELISA.Results: All three honeys stimulated TNF-α release from THP-1 cells, with kanuka honey being the most active. The activity of kanuka honey was associated with a high molecular weight (>30 kDa) component that was partially heat labile and inhibitable with polymyxin B. LPS concentrations in the honeys were too low to adequately explain the level of immunostimulation. The contr...
57 citations
TL;DR: The essential oil from the A. graveolens leaves was investigated for scavenging of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the results demonstrate that the essential oil has potential as a natural antioxidant and thus inhibit unwanted oxidation process.
Abstract: The leaves of Apium graveolens were extracted and the essential oil composition, immunotoxicity effects, and antioxidant activity were studied. The analyses were conducted by gas chromatography and mass spectroscopy (GC-MS), which revealed the essential oils of A. graveolens leaves. Twenty-eight components, representing 73.72% of the total oil were identified from the leaves. The major components are 4-chloro-4,4-dimethyl-3-(1-imidazolyl)-valerophenone (19.90%), 1-dodecanol (16.55%), 9-octadecen-12-ynoic acid, methyl ester (4.93%), ethyl 4,4-D2-N-hexyl ether (4.11%), 3-(hydroxymethyl)-1-phenyl-1-heptadecyn-3-ol (3.28%), 1,4-methano-1H-indene, octahydro-4-methyl-8-methylene-7-(1-methylethyl)-, [1S-(1α,3αα,4α,7α,7αα)]- (2.99%), 3,4-dihydro-2H-1,5-(3″-t-butyl)benzodioxepine (2.56%), Z-10-tetradecen-1-ol acetate (2.53%), 9H-pyrrolo[3',4':3,4]pyrrolo[2,1-α]phthalazine-9, 11(10H)-dione, 10-ethyl-8-phenyl (2.07%). The leaf oil had significant toxic effects against the larvae of A. aegypti with an LC(50) value of 59.32 ppm and an LC(90) value of 127.69 ppm. The essential oil from the A. graveolens leaves was investigated for scavenging of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the results demonstrate that the essential oil from the A. graveolens has potential as a natural antioxidant and thus inhibit unwanted oxidation process. The above data indicate that the major compounds may play an important role in the toxicity of essential oils and also as natural antioxidant.
50 citations
TL;DR: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity.
Abstract: Context: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations.Objective: This review presents and discusses current evidence on the safety of anti-TNFα agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance.Methods: Key studies on the safety of anti-TNFα agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA)...
49 citations
TL;DR: It is demonstrated that fisetin exerted anti-inflammatory activity via inactivation of JNK and NF-κB in LPS-stimulated macrophage cells.
Abstract: Although fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in the present study, the anti-inflammatory mechanism of fisetin was investigated in association with mitogen-activated protein kinase (MAPK) and nuclear factor κ B (NF-κB) pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages. We found that fisetin significantly reduced the nitrate oxide (NO) production and also inhibited the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) at protein and mRNA levels in LPS-stimulated cells. Consistently, fisetin significantly reduced the LPS-stimulated secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α). Furthermore, fisetin suppressed the activation of nuclear factor κ B (NF-κB) and the phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal regulated kinase (ERK) and p38 MAPK in LPS-treated RAW264.7 cells. Overall, our findings demonstrate that fisetin exerted anti-inflammatory activity via inactivation of JNK and NF-κB in LPS-stimulated macrophage cells.
49 citations
TL;DR: Results suggest that β-catenin plays a role as a negative regulator, preventing the overproduction of inflammatory cytokines such as IL-6 in LPS-induced inflammatory responses.
Abstract: In the present study, we investigated the possibility that the WNT/β-catenin pathway plays a role in inflammatory responses both in an human inflammatory condition and in an in vitro inflammation model. First, we analyzed gene expression patterns of the peripheral blood cells from asthma patients compared with those from normal subjects using microarray analyses. We found that intracellular signaling molecules of the WNT/β-catenin pathway were significantly changed in asthma patients compared with the levels in the controls. Next, we determined whether major components of the WNT/β-catenin pathway were involved in the lipopolysaccharide (LPS)-induced inflammatory response of the RAW264.7 macrophage cell line. Among the members of WNT/β-catenin pathway, the protein levels of low-density lipoprotein receptor-related protein (LRP) 6, dishevelled (DVL) 2, and AXIN1, which were measured using western blotting, did not significantly change in the presence of LPS. In contrast, the LPS induced a rapid phosphorylation of glycogen synthase kinase (GSK) 3β and accumulation of β-catenin protein. It was found that β-catenin plays a significant role in the LPS-induced inflammatory response through the performance of small interfering RNA (siRNA) transfection experiments. The mRNA level of IL-6 was significantly elevated in β-catenin siRNA-transfected cells compared with that in control siRNA-transfected cells after LPS treatment. Furthermore, nuclear factor-κB (NF-κB) activity was also significantly increased in β-catenin siRNA-transfected cells compared with the level seen in control siRNA-transfected cells. Taken together, these results suggest that β-catenin plays a role as a negative regulator, preventing the overproduction of inflammatory cytokines such as IL-6 in LPS-induced inflammatory responses.
48 citations
TL;DR: The results of this study indicate that parsley essential oil may be able to suppress the cellular and humoral immune response and can also suppress both NO production and the functions of macrophages as the main innate immune cells.
Abstract: Introduction: Parsley (Petroselinum crispum) has been traditionally used for the treatment of allergy, autoimmune and chronic inflammatory disorders. The present study aims to investigate the suppressive effects of parsley essential oil on mouse splenocytes and macrophages cells.Methods and Materials: Parsley essential oil was harvested. It was treated on splenocytes and phytohemagglutinin (PHA) (5 μg/mL) and lipopolysaccharide (LPS) (10 μg/mL) activated splenocytes in different concentrations (0.01–100 μg/mL); then, proliferation was assayed by methyl tetrazolium (MTT) method. Treatment was also performed on the macrophages and LPS-stimulated macrophages (10 μg/ml) and the nitrite levels were measured using the diazotization method based on the Griess reaction and MTT assay for evaluation of the viability of the macrophages.Results: Proliferation of splenocytes in all the treated groups was suppressed. In PHA-stimulated splenocytes, the suppression was seen in all the examined concentrations (0.01–100 μg...
47 citations
TL;DR: Identifying the new factors that induce stable phenotype in Tregs and prevent their phenotype conversion into Th17 cells as well as targeting the factor, which can modulate their balance, are recommended as new targets in treatment of these diseases.
Abstract: Identifying the regulatory T cells (Tregs) and Th17 cells led to breaking the dichotomy of Th1/Th2 cells axis in immune responses involved in several autoimmune diseases It is now well known that Tregs and Th17 cells are main orchestra leaders in pathogenesis symphony of autoimmunity While Tregs are protective cells in autoimmune diseases, Th17 cells enhance the progression of autoimmune responses through induction of various pro-inflammatory reactions It seems that the progression of autoimmunity may be associated with increase in Th17 and decrease in Treg levels, so that skewed balance between Tregs and Th17 toward Th17 is a phenomenon, which could be observed during progression of several autoimmune diseases Although it is suggested that expansion and transfer of Tregs can be a new therapeutic target for autoimmune diseases, however, recent data about the phenotype conversion of Tregs into Th17 cells obligate us to more investigation on this approaching Thus, identifying the new factors that induce stable phenotype in Tregs and prevent their phenotype conversion into Th17 cells as well as targeting the factor, which can modulate their balance, might be recommended as a new promising therapeutic method for autoimmune therapy In this review, we try to clarify the factors, which can affect on this balance in various autoimmune diseases, as new targets in treatment of these diseases
43 citations
TL;DR: The findings suggest that ED is a novel blocker of CXCR4 expression and, thus, has enormous potential as a powerful therapeutic agent for metastatic cancer.
Abstract: Emodin (ED), an anthraquinone derivative, has been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and enhance chemotherapy. However, the detailed mechanism of ED related to the regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects cellular migration and invasion in prostate and lung cancer cells are not fully understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in promoting invasion and metastasis in tumors. Thus, novel agents that can downregulate CXCR4 expression have therapeutic potential in repressing cancer metastasis. Among ED and its derivatives, it is found that ED downregulated the expression of both CXCR4 and HER2 without affecting cell viability in tumor cells. The suppression of CXCR4 expression by ED was found to correlate with the inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells. Besides, neither proteasome inhibition nor lysosomal stabilization had any effect on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms unveiled that the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression and suppression of NF-κB activation. Overall, our findings suggest that ED is a novel blocker of CXCR4 expression and, thus, has enormous potential as a powerful therapeutic agent for metastatic cancer.
42 citations
TL;DR: Results indicated that salidroside possess a protective effect on LPS-induced ALI in mice.
Abstract: Salidroside is a major component extracted from Rhodiola rosea. In this study, we investigated protective effects of salidroside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. In the mouse model, we found that pretreatment with a single 120 mg/kg dose of salidroside prior to the administration of intratracheal LPS induced a significant decrease in the W/D ratio and mouse myeloperoxidase activity of lung, reduction protein concentration, the number of total cells, neutrophils and macrophages in the bronchoalveolar lavage fluid. In addition, salidroside also inhibited the production of several inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 (IL-6) and IL-1β, and the NF-κB DNA-binding activation after LPS challenge. These results indicated that salidroside possess a protective effect on LPS-induced ALI in mice.
TL;DR: It was observed that the macrophage cell line J774A.1 when treated with Tinospora cordifolia (guduchi) and LPS showed enhanced NADH-oxidase, NADPH- oxidase and myeloperoxid enzyme production as compared to macrophages treated with medium alone.
Abstract: It is believed that the enhanced microbicidal and tumoricidal capability of activated macrophages is related to the remarkable increase in the production of oxygen metabolites. Both the production of H2O2 and the oxidation of NAD(P)H are directly dependent upon NAD(P)H-oxidase. It has been established that the respiratory burst is due to activation of NAD(P)H-oxidase localised in the plasmalemma. Myeloperoxidase is believed to be involved in augmenting the cytotoxic activity of H2O2. It was observed that the macrophage cell line J774A.1 when treated with Tinospora cordifolia (guduchi) and LPS showed enhanced NADH-oxidase, NADPH-oxidase and myeloperoxidase production as compared to macrophages treated with medium alone. The direct drug treatment to J774A cells showed activation as assessed by biochemical assays. These results suggest that high NADH-oxidase, NADPH-oxidase and myeloperoxidase activities may account for tumoricidal and microbicidal properties via macrophage activation.
TL;DR: The results suggest that andrographolide induces apoptosis via inhibiting NF-κB-induced bcl-2-mediated survival signaling and modulating p53-induced caspase-3-mediated proapoptotic signaling.
Abstract: Cancer is a disorder characterized by uncontrolled proliferation and reduced apoptosis. Inducing apoptosis is an efficient method of treating cancers. In this study, we investigated the effect of andrographolide on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of andrographolide showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays also confirmed the observation. The proapoptotic genes p53, Bax, caspase-9, and caspase-3 were found upregulated in andrographolide-treated cells, whereas the antiapoptotic gene bcl-2 was downregulated. This study also reveals that andrographolide treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, an...
TL;DR: This study demonstrated for the first time that NSAIDs, such as diclofenac sodium, salicylate and indomethacin, exert inhibitory effects on thymocyte Kv1.3-channel currents.
Abstract: Lymphocytes predominantly express delayed rectifier K+-channels (Kv1.3) in their plasma membranes, and the channels play crucial roles in the lymphocyte activation and proliferation. Since nonsteroidal anti-inflammatory drugs (NSAIDs), the most commonly used analgesic and antipyretic drugs, exert immunomodulatory effects, they would affect the channel currents in lymphocytes. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of diclofenac sodium, salicylate and indomethacin on the channel currents in murine thymocytes and the membrane capacitance. Diclofenac sodium and salicylate significantly suppressed the pulse-end currents of the channel. However, indomethacin suppressed both the peak and the pulse-end currents with a significant increase in the membrane capacitance. This study demonstrated for the first time that NSAIDs, such as diclofenac sodium, salicylate and indomethacin, exert inhibitory effects on thymocyte Kv1.3-channel currents. T...
TL;DR: The finding that daily intake of HK L-137 enhances type I IFN production and host defense against influenza A virus infection in mice may be applied to at least two additional species.
Abstract: We have previously reported that oral administration of heat-killed Lactobacillus plantarum L-137 (HK L-137) stimulates innate immunity for production of type I interferon (IFN) which subsequently augments host defense against influenza A virus infection in mice. We here examined the effect of HK L-137 intake on type I IFN in humans. Sixteen subjects were randomly assigned to receive a tablet containing 10 mg of HK L-137 or a matching tablet for 8 weeks and the serum levels of type I IFN were examined before and after the first or second dose of the trivalent inactivated influenza vaccine. There were no differences in the seroresponse rate, the seroprotection rate and the geometric mean Ab titers after either the first or second dose of vaccine between the HK L-137 group and the control group. On the other hand, the levels of IFN-β were significantly higher in the HK L-137 group than in the control group before vaccination although the vaccination conferred little additional induction of IFN-β. We further...
TL;DR: Results indicate that CHE may provide an anti-inflammatory effect by attenuating the generation of excessive NO, PGE2, and ROS and by suppressing the expression of pro-inflammatory genes through the inhibition of NF-κB and JNK activity.
Abstract: The aim of this study was to investigate the anti-inflammatory properties of each fraction of Hericium erinaceus (HE). The ethanol extract from HE was partitioned with different solvents in the ord...
TL;DR: Investigation of the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats found that altered levels of hematological parameters were reverted to near normal levels and the free radical scavenging activity of the plant was further evidenced.
Abstract: Free radical stress leads to tissue injury and progression of disease conditions such as arthritis, hemorrhagic shock, atherosclerosis, diabetes, hepatic injury, aging and ischemia, reperfusion injury of many tissues, gastritis, tumor promotion, neurodegenerative diseases and carcinogenesis. Safer anti-oxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders. Herbal medicine provides a foundation for various traditional medicine systems worldwide. The Sida species is one of the most important families of medicinal plants in India. Hence, the present study was aimed to investigate the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats. The altered levels of hematological parameters were reverted to near normal levels, especially the elevated rate of erythrocyte sedimentation was significantly reduced by S. rhombifolia extracts in experimental rats. Oral administration of root...
TL;DR: PEGylation is effective in reducing the immunogenicity, immunotoxicity, and hepatotoxicity of α-MMC in vivo.
Abstract: Background and aim: α-momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP) from Momordica charantia, is well known for its antitumor and antivirus activities. However, the immunotoxicity and hepatotoxicity hampers its potential therapeutic usage. In order to reduce its toxicity, we had modified the α-MMC with polyethylene glycol (PEG), and detected the toxicity of the PEGylated α-MMC conjugates (α-MMC-PEG) in vivo.Materials and methods: After α-MMC purified from bitter melon seeds, α-MMC-PEG was constructed with a branched 20 kDa (mPEG) 2-Lys-NHS, the tests of immunogenicity, immunotoxicity, and general toxicity of α-MMC-PEG were conducted in guinea pig and rat.Results: The titer of specific IgG in rats, immunized by α-MMC-PEG, were approximately one-third of those that by α-MMC, all the guinea pigs treated with α-MMC died of anaphylaxis shock within 5 min, while no animals treated with α-MMC-PEG died in the active systemic anaphylaxis (ASA) test. The passive cutaneous anaphylaxis (PCA) react...
TL;DR: It is demonstrated that LcS does not exacerbate EAE, but instead may improve EAE depending on the immunization conditions, and that IL-17 responses at peripheral sites may not always result in a worsening of autoimmune diseases.
Abstract: Context: It is of great importance to evaluate the safety of probiotics in dysregulated immune conditions, as probiotics can possibly modulate immune functions in the host.Objective: We tried to confirm the safety of using Lactobacillus casei strain Shirota (LcS) to help prevent autoimmunity in the central nervous system.Methods: We used two chronic experimental autoimmune encephalomyelitis (EAE) models, a relapse and remission type EAE model in SJL/J mice and a durable type model in C57BL/6 mice. LcS was administered from 1 week before antigen sensitization until the end of the experiments, and neurological symptoms and histopathological changes of the spinal cord were observed. Immunological parameters were also examined in the SJL/J mouse model.Results: LcS administration did not exacerbate neurological symptoms or histopathological changes of the spinal cord in either model but instead tended to improve neurological symptoms in the SJL/J mouse EAE model. LcS administration transiently upregulated IL-1...
TL;DR: The findings suggest the involvement of NO in experimental UC pathogenesis and pre- and pro-biotics, as discussed herein, seem to have an anti-inflammatory effect.
Abstract: Inflammatory bowel disease (IBD) consists mainly of Ulcerative colitis (UC) and Crohn disease (CD). Although its aetiology is still not clearly established, it is thought to be due to overly aggressive immune response to enteric bacteria in genetically predisposed individuals. Manipulating the microbiota using probiotics or prebiotics is considered as a promising field of new therapeutic strategies used to attenuate immune disorders observed during IBD. The production of nitric oxide (NO) seems to be implicated in IBD pathogenesis. In our study, an acute UC was induced in Swiss mice using 3% Dextran Sulfate Sodium (DSS). The preventive effects of “Ultrabiotique®” (a probiotic) and inulin (a prebiotic) on the colitis were investigated. The production of NO was evaluated in the supernatants of peritoneal macrophages (pMφ) cultures. Colonic mucosa histology was subsequently examined. Results showed severe acute UC after administration of DSS. High levels of NO in pMφ cultures were also observed compared to c...
TL;DR: Observations indicate that AGF display immunoadjuvant activity for a test antigen though the humoral immune response is delayed, similar to other adjuvants shown to possess immunomodulatory activities in vitro.
Abstract: Garlic (Allium sativum) is known for its innumerable biological activities including immunomodulation. Aged garlic extract (AGE), an odorless garlic preparation, has been shown to have superior immunomodulatory properties over raw garlic extract. Although garlic is a very rich source of fructans (17%, fresh weight basis), AGE contains only 0.22% of raw garlic fructans. Aged garlic fructans (AGF) have recently been shown to possess immunomodulatory activities in vitro. Natural adjuvants capable of eliciting better immune response of a model antigen are important in developing newer vaccines. In the present study, the adjuvant activity of AGF has been investigated in BALB/c mice using ovalbumin (OVA, 30 µg) as an experimental antigen. The body weights of animals did not change significantly indicating that the administration of garlic fructans is well-tolerated. AGF produce a significant humoral (serum IgG) response to OVA in BALB/c mice administered mucosally by either intranasal or oral route--a delayed response appearing on 50th day at a dose of 30 µg AGF by intranasal route. However, the serum IgG response was seen earlier on 35th day at a dose of 100 µg AGF by oral route. Higher concentrations of AGF (>50 µg) were inhibitory for adjuvant activity by intranasal administration. These observations indicate that AGF display immunoadjuvant activity for a test antigen though the humoral immune response is delayed.
TL;DR: The results suggested that clozapine and haloperidol may induce different immunomodulatory effects on the immune system.
Abstract: Antipsychotic drugs (APDs) are widely used to alleviate a number of psychic disorders and may have immunomodulatory effects. However, the previous studies of cytokine and immune regulation in APDs are quite inconsistent. The aim of this study was to examine the in vitro effects of different ADPs on cytokine production by peripheral blood mononuclear cells (PBMCs). We examined the effects of risperidone, clozapine, and haloperidol on the production of phorbol myristate acetate and ionomycin-induced interferon-γ (IFN-γ)/interleukin (IL)-4 in PBMCs by using intracellular staining. Real-time quantitative PCR and Western blot were used to further examine the expression changes of some critical transcription factors related to T-cell differentiation in antipsychotic-treated PBMCs. Our results indicated that clozapine can suppress the stimulated production of IFN-γ by 30.62%, whereas haloperidol weakly enhances the expression of IFN-γ. Differences in IL-4 production or in the number of CD4+ T cells were not observed in cells treated with different APDs. Furthermore, clozapine and risperidone inhibited the T-bet mRNA and protein expression, which are critical to Th1 differentiation. Also, clozapine can enhance the expression of Signal Transducer and Activator of Transcription 6 and GATA3, which are critical for the differentiation of Th2 cells. The results suggested that clozapine and haloperidol may induce different immunomodulatory effects on the immune system.
TL;DR: It is demonstrated for the first time that propolis inhibited IL- 6 plus transforming growth factor-β induced Th17 differentiation in vitro and suppressed the IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a cytokine-activated essential transcription factor in Th17 development.
Abstract: Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. It has been reported to show immunomodulatory activity. Previously, we reported the protective effect of Brazilian propolis ethanolic extract against the pathogenesis of collagen-induced arthritis (CIA), an experimental animal model of rheumatoid arthritis (RA). Moreover, we found that the protective effect against CIA was involved in suppression of the production of interleukin-17 (IL-17) in CIA mice. In the present study, we demonstrated for the first time that propolis inhibited IL-6 plus transforming growth factor-β induced Th17 differentiation in vitro. Propolis also suppressed the IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a cytokine-activated essential transcription factor in Th17 development, concomitantly with the enhanced suppressor of cytokine signaling 3 expression involved in the downregulation of STAT3 phosphorylation. These data suggest that the suppressive effect of propolis on Th17 differentiation might be useful for controlling unbalanced cytokine networks in autoimmune diseases.
TL;DR: Both LP and TM are safe by themselves and their composite succeeded to exert a potential prevention by counteracting ZEA-immunotoxicity and can be implicated in the biotechnology of ZEA removal in human food and animal feed.
Abstract: Background and aim: The present study was conducted to determine the abilities of the living Lactobacillus plantarum MON03 (LP) cells, Tunisian montmorillonite clay and their composites to accumulate Zearalenone (ZEA) from a liquid medium and elucidate the preventive effect of their composite in ZEA-contaminated balb/c mice showing immunotoxicity disorders.Materials and methods: In the in vitro study, LP (2 × 109 CFU/mL), TM (0.5 mg) and LP+TM were incubated with 50 µg mL−1 ZEA for 0, 12 and 24 h. For the in vivo study, the composite MT+LP was evaluated also for possible protection regarding ZEA-immunotoxicity in Balb/c mice as a sensitive model.Results: Results indicated that TM and LP+TM had a high capacity of adsorbing ZEA 87.2 ± 2.1 and 94.2 ± 2.1%, respectively. However, LP alone able to remove only 78% after 24 h of incubation. The quantity of adsorbed ZEA by LP, TM and LP+TM were 39, 43,5 and 47 µg mL−1 of PBS, respectively. The in vivo results indicated that mice orally exposed to ZEA- (40 mg/kg b...
TL;DR: Findings suggest that isorhamnetin 3-О-β-D-glucopyranoside exerts antiadipogenic activity through AMPK activation, as potent candidate of antiobesity agent via alleviation of lipid accumulation.
Abstract: In the present study, effect of flavonoid glucopyranoside, isorhamnetin 3-О-β-D-glucopyranoside, from Salicornia herbacea on adipogenic differentiation were evaluated in 3T3-L1 adipocytes. Confluent 3T3-L1 preadipocytes in medium (0.5 mM methylisobutylxanthine, 0.25 µM dexamethasone, 5 µg/mL insulin, and 10% fetal bovine serum [FBS]) were differentiated into adipocytes for 6 days with/without isorhamnetin 3-О-β-D-glucopyranoside. The presence of isorhamnetin 3-О-β-D-glucopyranoside effectively suppressed adipogenic differentiation by downregulation of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding proteins (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), and the adipocyte-specific proteins. Moreover, the specific mechanism mediating the effects of isorhamnetin 3-О-β-D-glucopyranoside was confirmed by activation of AMP-activated protein kinase (AMPK). These findings suggest that isorhamnetin 3-О-β-D-glucopyranoside exerts antiadipogenic activity through AMPK act...
TL;DR: Berberine, given orally at 40, 20, 10 mg/kg for 10 days, ameliorated all the supposed inflammatory symptoms of the induced colitis, and the results suggest that the protective effects of berberine against the DSS-induced colitis may be associated with the regulation of cytokine production.
Abstract: The anti-inflammatory effect of berberine was evaluated in murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Berberine, given orally at 40, 20, 10 mg/kg for 10 days, ameliorated all the supposed inflammatory symptoms of the induced colitis, such as body weightloss, blood hemoglobin reduction, high myeloperoxidase levels, and malondialdehyde content-inflamed mucosa. Furthermore, the cytokine production of splenic lymphocytes was analyzed. The results showed the IFN-γ and IL-12 were increased, but IL-4 and IL-10 were decreased in DSS-induced colitis,when those were compared with the normal control. But the administration of berberine to DSS-induced colitis mice showed lower production of IFN-γ and IL-12 and higher production of IL-4 and IL-10 than the DSS-induced colitis mice. The results suggest that the protective effects of berberine against the DSS-induced colitis may be associated with the regulation of cytokine production.
TL;DR: It is suggested that ECW ameliorates hypertension and endothelial dysfunction via improvement of NO/cGMP signaling pathway in aortic tissue of rats fed with HFCD, suggesting a vascular protective role for this herb in the treatment and prevention of atherosclerotic vascular disease.
Abstract: Hypercholesterolemia increases the incidence of atherosclerosis and its pathologic complications. This study was performed to test the effect of an ethanol extract of Cynanchum wilfordii (ECW) on vascular dysfunction in rats fed with high fat/cholesterol diets (HFCD). Male rats were fed a HFCD consisting of 7.5% cocoa butter and 1.25% cholesterol, with or without 100, 200 mg/day/kg ECW. Rats fed with HFCD increased body weight associated with an increase in plasma low-density lipoprotein (LDL) cholesterol level. Chronic ECW treatment in HFCD-fed rats lessened LDL cholesterol and triglyceride levels as well as elevated high-density lipoprotein (HDL) cholesterol. Chronic ECW treatment recovered the HFCD-induced increase in systolic blood pressure, maintained smooth and soft intima endothelial layers by the decrease of intima-media thickness. ECW significantly recovered the diet-induced decrease in vasorelaxation to acetylcholine, high-dose ECW apparently increased vasorelaxation response to sodium nitroprus...
TL;DR: Th17 cell differentiation, IL-17 levels, and TIM-3 regulation may be involved in the pathogenesis of GBS, and Tim-3 may inhibit Th17 cell activation, thereby modulating their cytokine secretion patterns.
Abstract: Objective and design: We investigated the involvement of Th17 cells and T-cell immunoglobulin and mucin domain 3 (TIM-3) in Guillain–Barre syndrome (GBS) in comparison to healthy subjects.Materials and subjects: Peripheral blood samples were obtained from 29 healthy subjects and 29 GBS patients.Treatment: Peripheral blood mononuclear cells (PBMCs) and CD4+ T cells were stimulated with anti-CD3 and anti-CD28 mAbs, in the absence or presence of anti-TIM-3 mAb.Methods: mRNA levels of TIM-3 and the transcription factor retinoic acid-related orphan receptor γt (RORγt) were determined by RT-PCR and were expressed relative to β-actin mRNA (housekeeping gene). Serum IFN-γ and IL-17 levels were determined by ELISA.Results: Compared to controls, relative TIM-3 mRNA levels were lower in both stimulated and unstimulated PBMCs from GBS patients. Unstimulated GBS CD4+ T cells and GBS CD4+ T cells stimulated with anti-CD3 and CD28 mAbs had higher relative RORγt mRNA expression compared to controls. GBS CD4+ T cells secr...
TL;DR: Results indicate that the immunostimulatory activities of RGE and BGE can be strongly correlated with the antioxidant and anticancer activities.
Abstract: The immunostimulatory activities of garlic extract using a cell line or animal models have been reported; however, no previous studies have evaluated individual differences in regards to the immunostimulatory activities The immunostimulatory activities such as cell proliferation, tumor necrosis factor (TNF-α) and nitric oxides (NO) production of raw garlic and black garlic extracts on individual primary lymphocytes or macrophages isolated from the blood of 21 volunteers were evaluated The antioxidant and anticancer effects of raw garlic and black garlic ethanol extract was measured to determine the optimum conditions for extraction The 70% ethanol black garlic extracts at 70°C for 12 h (70% BGE) showed the strongest antioxidant and anticancer activities Immunostimulatory activities of garlic extracts extracted under optimal condition on primary immune cells obtained from 21 volunteers were analyzed Results showed that the cell proliferation, TNF-α and NO production of primary immune cells treated wit
TL;DR: β-Thalassemia trait accompaniment to autoimmune disease may be the result of haplotypal associations between the close proximity genes, and Hemorphins are endogenous opioid peptides derived via proteolytical cleavage of hemoglobin that may explain a proinflammatory stage and autoimmunity vulnerability.
Abstract: Thalassemia major continues to be a significant health problem for Mediterranean, Afro-Arabic countries, India and South Easth Asia. It was generally assumed that the β-thalassemia heterozygotes do not bear significant medical risks except a mild microcytic anemia. Nonetheless, increasing number of reports associate β-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia and asthma. Available sparse data indicate reduced incidence of systemic lupus erythematosus (SLE) in β-thalassemia heterozygotes; yet, if two conditions coexist, the SLE manifestations occur much severer. These associations make sense when considering that the hemoglobin β-chain locus at 11p15.5 resides in close proximity to eight genes with profound roles in immune regulation: STIM1, CD151, TC21/RRAS2, SIGIRR/TOLL/IL1R8, pp52/LSP1 (lymphocyte specific protein), TRIM21, toll interacting protein (TOLLIP) and SLEN3. β-Thalassemia trait accompaniment to autoimmune disease may be the result of haplotypal associations between the close proximity genes. An alternative explanation to thalassemia heterozygosity: autoimmune disease association may be the changed concentrations of hemorphins. Hemorphins are endogenous opioid peptides derived via proteolytical cleavage of hemoglobin. They are shown to bind diverse opioid receptors and act anti-inflammatory. Their reduced expression in thalassemia heterozygosity may explain a proinflammatory stage and autoimmunity vulnerability.