Expression Of Immune Cytokines Research Articles

Immunostimulatory Effects of Red Beet Ferment Extract on Cyclophosphamide-Induced Immunosuppression in Wistar Rats

Red beet extract contains a variety of bioactive compounds, including antioxidant and immune-stimulating properties. Red beets are rich in nutrients and have been reported to help mitigate cardiovascular disease, while also possessing potent antioxidant capacity. In this study, we sought to determine the immune-enhancing effects of red beet fermented extract. The immunosuppressive drug cyclophosphamide (Cy) and red beet fermented extract were orally administered to Wistar rats once daily for four weeks. Blood analysis was performed to measure the expression of immune cytokines. We also examined the immunostimulatory effects of red beet fermented extract by measuring the activity and viability of spleen cells and the expression of immune cytokines. The expression of immune cytokines in the blood and spleen cells was increased in the red beet fermented extract treatment group compared to that in the negative control group, which induced immunosuppression of cytokines. It also increased the activity of NK cells and improved the viability of spleen cells. In conclusion, red beet fermented extract increased the expression of immune cytokines and increased the activity of adipocytes and NK cells, confirming its immunostimulatory effect. Therefore, red beet fermented extract has the potential to be utilized as a nutraceutical ingredient to enhance immunity.

Holothuria leucospilota polysaccharides (HLP) ameliorate colitis rats via regulation of the metabolic profiling and TLR4/NLRP3 signaling pathways

AbstractRecently, the development of natural polysaccharides for ameliorating immunity and gut metabolism has attracted extensive attention. This study used Holothuria leucospilota polysaccharides (HLP) to explore the improvement mechanism in ulcerative colitis rats on perspectives of immunity and metabolism. The results showed that HLP increased goblet cells’ number and the content of tight junction proteins (zona occludens 1 and occludin) and improved intestinal barrier permeability. The levels of immune cytokines (IL‐4, IL‐6, IL‐10, IL‐18, TNF‐α, and IL‐1β) and the activity of oxidative stress‐related enzymes (superoxide dismutase, catalase, malondialdehyde, and glutathione peroxidase) were regulated. HLP regulated the related genes and proteins expression of immune cytokines, MAPK, and NLRP3 inflammasome. Furthermore, HLP treatment increased the concentration of short‐chain fatty acids (SCFAs) and regulated serum metabolic disorders by regulating amino acid metabolism, SCFA metabolism, and energy metabolism. These results provide a new perspective for developing HLP as a promising functional food for preventing and mitigating colitis.

Stress-associated β -glucan administration stimulates the TLR – MYD88 – NFKB1 signaling pathway in Nile tilapia (Oreochromis niloticus)

There is evidence that the administration of β-glucan can effectively activate several defense mechanisms, such as the Tlr-Myd88-Nfkb1 pathway that induces the expression of immune cytokines. Thus, the objective of this work was to evaluate whether β-glucan acts on the mechanisms of gene transcription via the Tlr-Myd88-Nfkb1 pathway in Nile tilapia under stress after challenge with Streptococcus agalactiae. Therefore, we evaluated the expression of immune system genes such as toll-like receptors 1 (tlr1), toll-like receptors 2 (tlr2), primary myeloid differentiation response gene (myd88) and nuclear factor kappa B1 (nfkb1). A total of 408 fish were distributed in 24 polyethylene boxes and randomly divided into eight groups with 3 replications each: C15: Tilapias received a control diet (free of β-glucan) for 15 days and were sampled after the 15th day of the experiment; C15D: Tilapias received a control diet (free of β-glucan) for 15 days, were challenged on the 14th day and were sampled at the 15th day of the experiment; β15: Tilapias received experimental diet (1g kg−1 of β-glucan) for 15 days and were sampled after 15 days; β15D: Tilapias received an experimental diet (1g kg−1 of β-glucan) for 15 days, were challenged on the 14th day and were sampled at the 15th day of the experiment; C30: Tilapias received a control diet (free of β-glucan) for 30 days and were sampled on the 30th day of the experiment; C30D: Tilapias received a control diet (free of β-glucan) for 30 days, were challenged on the 29th day and were sampled at the 30th day of the experiment; β30: Tilapias received experimental diet (1g kg-1 of β-glucan) for 30 days and were sampled after 30 days and β30D: Tilapias received experimental diet (1g kg−1 of β-glucan) for 30 days, were challenged on the 29th day and were sampled at 30 of the experiment. In the fish sampled at 15 and 30 days of the experiment, after being anesthetized and killed by brain section, cranial kidney and spleen were collected for gene expression analysis. The analyzes showed that the association of β-glucan and stressful management modulated the immune system, using the Tlr-Myd88-Nfkb1 signaling pathway, indicating that this compound can be used to promote early defense and protect fish against diseases.

Effects of levels of methionine supplementations in forms of L- or DL-methionine on the performance, intestinal development, immune response, and antioxidant system in broilers challenged with Eimeria spp.

The study was conducted to investigate the effects of 2 isoforms of methionine on growth performance and intestinal health induced by methionine (Met) deficiency and Eimeria infection in broilers. A total of 720 one-day old male chicks (Cobb500) were randomly allocated to 10 groups in a 2×5 factorial arrangement (6 reps/group, 12 birds/cage) with diets and Eimeria challenge as the main factors. Hundred percent DL-Met, 100% L-Met, 80% DL-Met, and 80% L-Met diets were formulated to meet approximately 100 or 80% of the total sulfur amino acid (TSAA) requirement with DL-Met or L-Met as Met supplementation sources. The 60% TSAA basal diet (60% Met) was formulated without Met supplementation. At d14, the challenge groups were gavaged with mixed Eimeria spp. Growth performance was recorded on d7, 14, 20 (6-day postinfection [DPI]), and 26 (12 DPI). The gut permeability was measured on 5 and 11 DPI. Antioxidant status and gene expression of immune cytokines and tight junction proteins were measured on 6 and 12 DPI. Data were analyzed by 1-way and 2-way ANOVA before and after the challenge, respectively. Orthogonal polynomial contrasts were used for post hoc comparison. Overall, the Eimeria challenge and 60% Met diet significantly reduced growth performance, antioxidant status, and mRNA expression of tight junction genes and immune cytokines. For other Met treatments, the L-Met groups had significantly higher BWG and lower FCR than the DL-Met group from d 1 to 20. The L-Met groups had less gut permeability than the DL-Met groups on 5 DPI. Compared to the 80% Met groups, the 100% Met groups reduced gut permeability. At 6 DPI, the 80% Met groups showed higher ZO1 expression than the 100% Met groups. The challenge groups had higher Muc2 expression and GSH/GSSG compared to the nonchallenge groups, and SOD activity was lower in the L-Met groups compared to the DL-Met groups at 6 DPI. The 100% Met groups had higher GPx activity than the 80% Met groups at 12 DPI. In conclusion, during coccidiosis, the 100% Met groups had better gut integrity and antioxidant status. Met supplementation in the form of L-Met improved growth performance in the starter phase and gut permeability in the challenge phase.

Anti-Inflammatory Agents: An Approach to Prevent Cognitive Decline in Alzheimer's Disease.

Systemic inflammation is an organism's response to an assault by the non-self. However, that inflammation may predispose humans to illnesses targeted to organs, including Alzheimer's disease (AD). Lesions in AD have pro-inflammatory cytokines and activated microglial/monocyte/macrophage cells. Up to this point, clinical trials using anti-amyloid monoclonal antibodies have not shown success. Maybe it is time to look elsewhere by combating inflammation. Neuroinflammation with CNS cellular activation and excessive expression of immune cytokines is suspected as the "principal culprit" in the higher risk for sporadic AD. Microglia, the resident immune cell of the CNS, perivascular myeloid cells, and activated macrophages produce IL-1, IL-6 at higher levels in patients with AD. Anti-inflammatory measures that target cellular/cytokine-mediated damage provide a rational therapeutic strategy. We propose a clinical trial using oral type 1 IFNs to act as such an agent; one that decreases IL-1 and IL-6 secretion by activating lamina propria lymphocytes in the gut associated lymphoid tissue with subsequent migration to the brain undergoing inflammatory responses. A clinical trial would be double-blind, parallel 1-year clinical trial randomized 1 : 1 oral active type 1 IFN versus best medical therapy to determine whether ingested type I IFN would decrease the rate of cognitive decline in mild cognitive impairment or mild AD. Using cognitive psychometrics, imaging, and fluid biomarkers (MxA for effective type I IFN activity beyond the gut), we can determine if oral type I IFN can prevent cognitive decline in AD.

The Mediation of miR-34a/miR-449c for Immune Cytokines in Acute Cold/Heat-Stressed Broiler Chicken.

Simple SummaryIn the intensive and scale poultry industry, the level of heat stress (HS) directly affects the growth, development, and production performance of poultry. To alleviate the adverse effects of stress in broilers, microRNA (miRNA) was regarded as a potential regulator of immune cytokines. In this study, through the sequencing analysis of spleens after cold/heat stress, we found that 33 and 37 miRNA were differentially expressed in the heat stress group compared with the normal (NS) group and cold stress (CS) group, respectively. The differential miRNA were mainly involved in biological processes such as the cytokine–cytokine receptor interaction. To further understand the miRNA-mediated effect of heat stress on the immune level of chickens, we selected miR-34a and miR-449c as the research objects, predicted and verified that interleukin 2 (IL-2) and interleukin 12α (IL-12α) were the target genes of miR-34a and miR-449c. Coupled with the analysis of the expression of other cytokines, we found that miRNA could change the expression of immune cytokines directly or indirectly. This discovery provides a new insight into the mediation of miRNA for immune cytokines in acute cold/heat stressed broiler chicken.An increasing amount of evidence has revealed that microRNAs (miRNAs) participated in immune regulation and reaction to acute cold and heat stresses. As a new type of post-transcriptional regulatory factor, miRNA has received widespread attention; However, the specific mechanism used for this regulation still needs to be determined. In this study, thirty broilers at the same growth period were divided into three groups and treated with different temperature and humidity of CS (10–15 °C and 90% Relative Humidity (RH)), HS (39 °C and 90% RH), and NS (26 °C and 50–60% RH) respectively. After 6 h, splenic tissues were collected from all study groups. miRNA sequencing was performed to identify the differentially expressed miRNAs (DEMs) between HS, CS, and NS. We found 33, 37, and 7 DEMs in the HS-NS, HS-CS, CS-NS group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEMs were significantly enriched in cytokine–cytokine receptor interaction and functioned as the cellular responders to stress. We chose two miRNA, miR-34a and miR-449c, from the same family and differential expressed in HS-CS and HS-NS group, as the research objects to predict and verify the target genes. The dual-luciferase reporter assay and quantitative real-time PCR (qRT-PCR) confirmed that two cytokines, IL-2 and IL-12α, were the direct target genes of miR-34a and miR-449c. To further understand the mediation mechanism of miRNAs in acute cold/heat-stressed broiler chicken, a splenic cytokines profile was constructed. The results showed that IL-1β was strongly related to acute heat stress in broiler chicken, and from this we predicted that the increased expression of IL-1β might promote the expression of miR-34a, inducing the upregulation of interferon-γ (INF-γ) and IL-17. Our finds have laid a theoretical foundation for the breeding of poultry resistance and alleviation of the adverse effects of stress.

The miR-155 regulates cytokines expression by SOSC1 signal pathways of fish in vitro and in vivo

MiR-155 is reported as immune regulated miRNA in mammalian corresponding to immunity, antibacterial and antiviral effects regulation. However, the roles and mechanisms of the miRNA have remained largely undefined. We herein comprehensively investigated the functions of miR-155 in vitro and in vivo by miR-155 mimics, agomir and antagomir in Cyprinus carpio and Ictalurus punctatus, with the target genes in the SOSC1 pathway certified in I. punctatus via luciferase reporter assays. Results showed that the miR-155 regulated the expressions of cytokines, including TNF-α, IFN-γ, IL-1β, IL-6 and IL-10. Further research confirmed SOSC1 as one of the targets of the miRNA, and the JAK1/STAT3/SOSC1 signal pathway involved in the miR-155 effects on the expression of immune cytokines as well. Additionally, the changes of TLR2 in fish may also be related to miR-155 along with its target SOCS1, and the TLR2/MyD88 pathway may partly participate in the effects of the miR-155 on the cytokines. The research here confirmed that the miR-155 can regulate cytokines expression by SOSC1 signal pathways of fish in vitro and in vivo, which would provide resources for understanding and studying about immune regulation in fish.

Exposure to microplastics impairs digestive performance, stimulates immune response and induces microbiota dysbiosis in the gut of juvenile guppy (Poecilia reticulata)

Microplastics (MPs) are widely distributing in aquatic environment. They are easily ingested by aquatic organisms and accumulate in digestive tract especially of intestine. To explore the potential effects of MPs on intestine, here we, using juvenile guppy (Poecilia reticulata) as experimental animal, investigated the response characteristics of digestion, immunity and gut microbiota. After exposure to 100 and 1000 μg/L concentrations of MPs (polystyrene; 32–40 μm diameters) for 28 days, we observed that MPs could exist in guppy gut and induce enlargement of goblet cells. Activities of digestive enzymes (trypsin, chymotrypsin, amylase and lipase) in guppy gut generally reduced. MPs stimulated the expression of immune cytokines (TNF-α, IFN-γ, TLR4 and IL-6). Through high throughput sequencing of 16S rRNA gene, decreases in diversity and evenness and changed composition of microbiota were found in guppy gut. PICRUSt analysis revealed that MPs might have effects on intestinal microbiota functions, such as inhibition of metabolism and repair pathway. Our findings suggested that MPs could retain in the gut of juvenile guppy, impair digestive performance, stimulate immune response and induce microbiota dysbiosis in guppy gut. The results obtained here provide new insights into the potential risks of MPs to aquatic animals.

NLRP3 inflammasome in immune cells regulates metastatic potential of cancer

Abstract One of the main features of tumor microenvironment is inflammation accompanied with the activation of immune cells and the production of pro-inflammatory cytokines. IL-1b, one of the critical cytokines released by immune cells to promote tumor growth and metastasis by acting on its receptor, IL-1R, and to culminate in the secondary activation of immune cells and the expression of immune cytokines. Inflammasome plays a critical role in production of mature IL-1b through activation of capspase-1. Therefore, we investigated whether regulation of NLRP3 inflammasome in macrophages affected the metastatic potential of tumor cells. Activation of NLRP3 inflammasome was induced by ATP in bone marrow-derived primary mouse macrophages. The metastatic potential of tumor cells was determined by transwell migration and invasion assays. Wild-type macrophages stimulated with ATP increased the migration and invasion of melanoma cells (B16F10). However, NLRP3- or caspase-1-knockout macrophages showed greatly decreased ability to promote the migration and invasion of melanoma cells. Treatment with celastrol, an inhibitor of NLRP3 inflammasome, blocked the ability of macrophages to stimulate migration and invasion of melanoma cells. The results show that inhibition of the NLRP3 inflammasome in macrophages by genetic deficiency or a pharmacological inhibitor leads to decrease of the metastatic potential of tumor cells. The results would provide a novel anti-cancer immuntherapy to regulate the activity of NLRP3 inflammasome in tumor microenvironment. [Supported by grants from BK21 PLUS program, NRF-2019R1A2C2085739, and NRF-2017R1A4A1015036].

Effect of Herbal Formulation on Immune Response Enhancement in RAW 264.7 Macrophages.

Immune response is a necessary self-defense mechanism that protects the host from infectious organisms. Many medicinal plants are popularly used in Asian folk medicine to increase body resistance. An herbal formulation named KM1608 was prepared from three medicinal plants: Saussurea lappa, Terminalia chebula, and Zingiber officinale. In this study, we evaluated the immune stimulatory effect of KM1608 on RAW 264.7 murine macrophages. Network pharmacological analyses were used to predict potential immune response pathways of major compounds from KM1608. The cytotoxicity and immuno-stimulating effect of KM1608 were determined using cell viability and nitric oxide assays. The underlying mechanism of immunomodulatory activity was evaluated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) of pro-inflammatory cytokines. The results of network pharmacological analysis suggested that major compounds from KM1608 possess anticancer potential via immune signaling pathways. After treatment with KM1608 at 25–100 µg/mL for 24 h, the level of nitric oxide was increased in the dose-dependent manner. The results of quantitative real-time PCR showed that KM1608 stimulates the expression of immune cytokines (interferon (IFN)-α, -β, IL-1β, -6, IL-10, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)) in macrophages. KM1608 extract is a potential agent for immune response enhancement.

Immunostimulatory activity of Y-shaped DNA nanostructures mediated through the activation of TLR9

Immunostimulatory oligodeoxynucleotides (DNAs) have been widely studied in pharmaceutical and biomedical research fields for applications in cancer immunotherapy and vaccination. Toll-like receptors (TLRs) are critical for the instruction and orchestration of the host immune system composed of innate and adaptive immunity. In particular, TLR9 responds to DNAs with unmethylated deoxycytosine-deoxyguanosine (CpG) motifs, thereby inducing the activation of innate immune cells, such as dendritic cells, and consequently, adaptive immune cells. In this study, we developed two kinds of Y-shaped double-stranded DNA nanostructures (Y-DNAs), including a single unit composed of three DNA strands (YS-DNA) and a ligated multiunit complex formed by crosslinking each YS-DNA (YL-DNA), and investigated whether they have immunostimulatory activity in innate immune cells. YS-DNA and YL-DNA induced the production of immune cytokines such as IL-12 and TNF-α and the expression of costimulatory molecules such as CD80 and CD86 in primary mouse dendritic cells and macrophage cells (RAW264.7 cells). A Coprecipitation study demonstrated that YL-DNA was directly associated with TLR9. The induction of immune cytokines by YS-DNA and YL-DNA was abolished in TLR9-deficient primary mouse dendritic cells. The results demonstrated that Y-DNAs induced the activation of dendritic cells and macrophages mediated by the activation of TLR9, as shown by the expression of immune cytokines and costimulatory molecules. The results suggest that Y-DNA nanostructures provide a beneficial strategy for immunotherapy by modulating the immune system.

Abstract 1936: The central role of NFAT signalling in the mechanism of action of the TRPV6 oncochannel inhibitor and clinical candidate SOR-C13

Abstract SOR-C13, a 13-mer peptide derived from soricidin, the paralytic peptide in saliva of the Northern Short-tailed shrew, has completed an open-label, all comers Phase I Clinical Trial for the treatment of epithelially-derived cancers. SOR-C13 is a first-in-class drug candidate for the treatment of solid tumors. SOR-C13 specifically targets and inhibits the TRPV6 calcium channel - a recognized oncochannel whose over-expression in a number of epithelial cancers (e.g. breast, ovarian, prostate) is associated with poor prognosis. An increase in TRPV6 facilitates calcium influx into the cell, which activates the calcium binding protein calmodulin. This complex in turn activates calcineurin that de-phosphorylates and activates Nuclear Factor of Activated T-cells (NFAT), a gene transcription factor involved in multiple oncogenic processes. To demonstrate the role of NFAT activation in the mechanism of action (MOA) of SOR-C13, breast cancer cells (T-47D) were transfected with a NFAT dual reporter plasmid, treated with the peptide, and NFAT activation monitored. Additionally, RT-qPCR TaqMan array profiling was performed on prostate (PC-3), breast (T-47D), ovarian (OVCAR-3 and SK-OV-3), and pancreatic (BxPC-3 and SU.86.86) cancer cell lines treated with SOR-C13 compared with untreated cells. The TaqMan array panel consisted of 187 genes involved in cancer calcium signalling associated with the MOA of TRPV6 and directly, or indirectly, involved in NFAT signalling. SOR-C13 treatment significantly inhibited NFAT activation (p < 0.05) in T-47D cells transfected with a NFAT reporter plasmid. Molecular profiling of the 6 cancer cell lines showed that many genes involved in NFAT signalling were modulated by SOR-C13 treatment. Affected genes included genes involved in cell proliferation (e.g. TGF-beta, TLR9), metastasis (e.g. ADAM12, CEACAM6), resistance to apoptosis (e.g. WISP1) and angiogenesis (e.g. FLT4). Cytokines (e.g. IL-6) and chemokines (e.g. CXCL12), involved in cancer progression and associated with NFAT signalling, as well as transcription factors (e.g. GATA4, NF-kB) were down regulated upon SOR-C13 treatment. These results highlight NFAT signalling in the mechanism of action of SOR-C13. The impact of SOR-C13 on the expression of genes involved in resistance to apoptosis, proliferation, metastasis and angiogenesis as well as on the expression of immune cytokines and transcription factors in multiple cancer cells, makes SOR-C13 an attractive, novel anti-cancer drug. Citation Format: Christopher Rice, Tyler Lutes, Michelle Davey, Vett Lloyd, Tyson J. MacCormack, John M. Stewart, Dominique Dugourd. The central role of NFAT signalling in the mechanism of action of the TRPV6 oncochannel inhibitor and clinical candidate SOR-C13 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1936.

Systemic delivery of the tumor necrosis factor gene to tumors by a novel dual DNA-nanocomplex in a nanoparticle system

Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector–cationic peptide nanocomplex (NC) surrounded by a diblock polymeric NP. Tumor necrosis factor alpha (TNF) was selected as the prototype cytokine for this system, based on its pleotropic inflammatory and anti-cancer activities. Our results demonstrate that the DNP system is highly effective in driving expression of TNF in tumor cells. We also demonstrate that the DNPs are effective in inducing apoptosis and anti-tumor activity. These findings support a novel immunotherapeutic approach for the intratumoral delivery of DNA vectors that express inflammatory cytokines.

X-shaped DNA potentiates therapeutic efficacy in colitis-associated colon cancer through dual activation of TLR9 and inflammasomes

BackgroundImmunotherapy has been extensively pursed as a promising strategy for the treatment of cancer. Pattern-recognition receptors (PRRs) play important roles in triggering activation of innate and adaptive immunity. Therefore, agents that stimulate PRRs could be useful for cancer immunotherapy. We developed two kinds of X-shaped double-stranded oligodeoxynucleotides (X-DNA), a single unit of X-DNA (XS-DNA) composed of four strands of DNA and a ligated X-DNA complex (XL-DNA) formed by crosslinking each XS-DNA to the other, and investigated if they had immunostimulatory activity and could be applied to anti-cancer immunotherapy.MethodsActivation of MAPKs and NF-κB was determined by immunoblotting in bone marrow-derived primary dendritic cells (BMDCs). Immune cytokines and co-stimulatory molecules were measured by ELISA and flow cytometry analysis. Anti-cancer efficacy was examined in an azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer mouse model. Association of X-DNA and TLR9 was determined by co-immunoprecipitation followed by immunoblotting. The involvement of TLR9 and inflammasomes was determined using TLR9- or caspase-1-deficient BMDCs. Inflammasome activation was examined by degradation of pro-caspase-1 to caspase-1 and cleavage of pro-IL-1β to IL-1β in BMDCs.ResultsXL-DNA and XS-DNA induced activation of MAPKs and NF-κB and production of immune cytokines and co-stimulatory molecules in BMDCs. BMDCs stimulated by XL-DNA induced differentiation of naïve CD4+ T cells to TH1 cells. Intravenous injection of XL-DNA into mice resulted in increased serum IFN-γ and IL-12 levels, showing in vivo efficacy of XL-DNA to activate TH1 cells and dendritic cells. XL-DNA greatly enhanced the therapeutic efficacy of doxorubicin, an anti-cancer drug, in colitis-associated colon cancer. XL-DNA directly associated with TLR9. In addition, immunostimulatory activities of X-DNA were abolished in TLR9-deficient dendritic cells. Furthermore, X-DNA induced caspase-1 degradation and IL-1β secretion in BMDCs, which were abolished in caspase-1-deficient cells.ConclusionsX-DNA induced the activation of dendritic cells as shown by the expression of immune-cytokines and co-stimulatory molecules, resulting in the differentiation of TH1 cells, mediated through dual activation of TLR9 and inflammasomes. X-DNA represents a promising immune adjuvant that can enhance the therapeutic efficacy of anti-cancer drugs by activating PRRs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0369-2) contains supplementary material, which is available to authorized users.

Effects of selenium and cadmium on changes in the gene expression of immune cytokines in chicken splenic lymphocytes.

Cadmium (Cd) is an environmental pollutant that is considered to be a potent toxin to organisms. Selenium (Se) has been known for its concomitant biological effects and characteristics with Cd. Due to the lack of the research regarding how the duality of Cd/Se affects immune cytokines in poultry, this paper aims to partly tackle this question. Chicken splenic lymphocytes with Cd (10(-6)mol/L CdCl2), Se (10(-7)mol/L Na2SeO3), Cd + Se (10(-7)mol/L Na2SeO3 and 10(-6)mol/L CdCl2), and a control group were incubated for 12, 24, 36, 48, and 60h, respectively. At each time point, the cells were collected and the messenger RNA (mRNA) expression levels of interleukin (IL)-1β, IL-2, IL-4, IL-10, IL-17, and interferon-γ (IFN-γ) were also examined. Compared with the control group and the Se-alone-treated group, the mRNA expression levels of IL-2, IL-4, IL-10, IL-17, and IFN-γ decreased significantly in the Cd-alone-treated group. By contrast, the mRNA expression level of IL-1β markedly increased. Levels of IL-2, IL-4, IL-10, IL-17, and IFN-γ in Cd + Se-treated groups were significantly higher than those in Cd-alone-treated groups; however, the levels were not as high as the Se-alone-treated groups and the control group. The mRNA expression level of IL-1β in the Cd + Se-treated group was lower than in the Cd-alone-treated group. The relationships with IL-2, IL-4, and IL-10 were found to be closer in the PC 1 matrix and 3D plot of the principal component analysis (PCA) loadings. IL-17 and IFN-γ were closer in the matrix of PC 2. However, IL-1β gene expression appeared to be isolated in the matrix of PC 3. In addition, the results of cytokine cluster analysis showed that IL-2, IL-4, IL-10, IL-17, and IFN-γ were in the first group and that IL-1β was in the second group. Therefore, Se partly attenuate immune toxicity induced by Cd in chicken splenic lymphocytes.