TNF-α In Spleen Research Articles

Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever

Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever. The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E2 (PGE2) surges, and hypothalamic PGE2 (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α. These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE2 production, possibly in a corticosterone- and inflammatory reflex-dependent manner.

Probiotic Efficacy in Aquaculture: The Role of Technospore® (Bacillus coagulans) in Improving Nile Tilapia (Oreochromis niloticus) Performance and Disease Resistance: a Study on Gut Health, Immunological Response, and Gene Expression.

This study evaluated the effects of Technospore® (Bacillus coagulans) supplementation on intestinal health, immune response, and Oreochromis niloticus (Nile tilapia) growth performance. The experiment divided fish into four groups: a control group fed an unsupplemented diet and three experimental groups receiving diets supplemented with 0.2g/kg, 0.4g/kg, and 0.8g/kg of Technospore®, respectively. Results indicated that Technospore® supplementation significantly enhanced growth rates and feed efficiency in all treated groups, with the most pronounced improvements observed in the group receiving 0.4g/kg. Furthermore, the study revealed that B. coagulans supplementation markedly boosted serum immune responses, as evidenced by increased phagocytic activity, phagocytic index, and lysozyme levels, following a challenge with Aeromonas hydrophila. Histological analysis showed improved gut morphology, while gene expression analysis indicated upregulation of immune-related genes, including liver IGF-1, GHR, HSP70, IL-1β, and TNF-α, as well as spleen TNF-α and IL-1β and intestinal C-lysozyme and TNF-α, both before and after the bacterial challenge. These findings suggest that dietary inclusion of Technospore® can significantly improve gut health and immune responses in tilapia, potentially serving as an effective prophylactic alternative to antibiotics in aquaculture.

Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis

Background: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary system. Glutathione (GSH) enhances endothelial response and prevents liver fibrosisObjectives: This study evaluates the effect of a combination of GSH-UDCA on splenic TNF-α expression and apoptosis index in Sprague Dawley (SD) rats with cholestasisMethods: This experiment with a post-tests-only control group design involving 28 male SD rats. They were randomly into four groups: group (K) with 20 mg UDCA, group 1 (P1) with 10 mg UDCA + 10 mg GSH, group 2 (P2) was given UDCA 20 mg + GSH 15 mg, and group 3 (P3) was given UDCA 30 mg + GSH 20 mg. Cholestasis was obtained by ligation of the common bile duct through a laparotomy. During three weeks of trial, rats were administered daily with UDCA orally and GSH intramuscularly. On day 22, rats were sacrificed and spleen samples were taken for anatomical pathology examination. Results: There were significant differences in TNF-α expression between groups K vs P3; P1 vs P3, and P2 vs P3 (p=0.002). There was a significant difference in the apoptotic index between groups K vs P1 (p<0.001); K vs P2 (p=0.004), and K vs P3 (p=0.005).Conclusions: The UDCA-GSH combination demonstrated a prophylactic effect in SD rats with cholestasis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The difference in TNF-α expression and apoptotic index was lower in SD rats UDCA-glutathione combination group than single dose UDCA. Between TNF-α and the apoptotic index, there is a moderate positive relation.

Heat‐killed Pseudoalteromonas piscicida 2515 decreased bacterial dose and improved immune resistance against Vibrio anguillarum in juvenile olive flounder ( Paralichthys olivaceus )

The Pseudoalteromonas piscicida 2515 is a potent probiotic with broad effect against Vibrio bacteria. Juvenile olive flounder (Paralichthys olivaceus) (9.04 ± 0.89 g) were used to evaluate the safety of P. piscicida 2515 (control, 106, 107, 108 and 109 CFU/g) in terms of haemolysis activity and mortality rate. To investigate the effects of P. piscicida 2515 (live and heat-killed) on the immune response, and intestinal microbiota and morphology in olive flounder (24.72 ± 2.21 g), five treatment groups, including control, L5 (live bacteria, 105 CFU/g), L7 (live bacteria, 107 CFU/g), HK5 (heat-killed bacteria, 105 CFU/g) and HK7 (heat-killed bacteria, 107 CFU/g), were set up over 35 days. The results showed that treatment with 109CFU/g live P. piscicida 2515 could lead significantly high haemolytic activity. Live- and heat-killed- P. piscicida 2515 significantly increased peroxidase (POD) and serum lysozyme (LZS) activities, while heat-killed P. piscicida 2515 increased SOD and TP. Moreover, L7 could increase expressions of IL-1β and TNF-α in kidney, whereas HK5 could raise IL-10 and TNF-α in spleen, and upregulate IL-1β in kidney. P. piscicida 2515 modulated microbiota richness (Ace and Chao1) and composition at the phylum level. In addition, supplementation of P. piscicida 2515 (live- and heat-killed) could significantly raise intestinal goblet cell number and microvilli length (p < 0.05). Particularly, fish in the treatment groups of HK5 and L7 exhibited higher survival rate against V. anguillarum infection. Therefore, P. piscicida 2515 demonstrated probiotics potency at 108 CFU/g or less based on feed supplement, and heat-killed (105 CFU/g) P. piscicida 2515 has decreased probiotic level dose and has improved the non-specific immunity, intestinal function and protected the olive flounder against V. anguillarum.

Immunoenhancement Effects of the Herbal Formula Hemomine on Cyclophosphamide-Induced Immunosuppression in Mice

Hemomine is an herbal blend comprising Angelicae Gigantis Radix and other herbs known to have immunomodulatory effects. We examined the immunopotentiating effect of this herbal blend on cyclophosphamide (CPA)-induced immunosuppression. Male mice were assigned to one of six groups: the intact control and five CPA treatment groups (one control, one reference (β-glucan), and three with the application of hemomine at different concentrations; 4, 2, or 1 mL/kg; n = 10 per group). Mice were injected with CPA to induce myelosuppression and immunosuppression, after which they received one of the experimental treatments. In immunosuppressed mice, hemomine treatment alleviated the noticeable reductions in body, spleen, and submandibular lymph node weights caused by CPA; caused changes in hematological markers; induced the reduced levels of serum IFN-γ and spleen TNF-α, IL-1β, and IL-10 by CPA; improved natural killer cell activities in the spleen and peritoneal cavity; and also improved lymphoid organ atrophy in a dose-dependent manner. We demonstrate that hemomine, a mixture of six immunomodulatory herbs, is an effective immunomodulatory agent, with the potential to enhance immunity.

Effects of Vitamin A and K3 on Immune Function and Intestinal Antioxidant Capacity of Aged Laying Hens

This study was conducted to investigate effects of vitamin A (VA) and vitamin K3 (VK3) on immune function and intestinal antioxidant capacity of aged laying hens. In a 3 × 3 factorial arrangement, the diets of 1080 Roman Pink laying hens (87 weeks old) was formulated with deficient, adequate and excess VA and VK3, including 0, 7000 and 14000 IU/kg VA and 0, 2.0 and 4.0 mg/kg VK3 for 8 weeks. Interactive effects between VA and VK3 were observed that VA and VK3 decreased the splenetic mRNA expression of inducible nitric oxide synthase (iNOS) and tumour necrosis factor α (TNF-α), but increased the plasma immunoglobulin G (IgG) content and jejunal mRNA expression of nuclear factor-like 2 (Nrf2). Hens fed adequate or excess VA had higher spleen index, mRNA expression of interleukin-10 (IL-10) in spleen, sIgA content, catalase (CAT), glutathione peroxidase and total dismutase (T-SOD) activity, and mRNA expression of polymeric immunoglobulin receptor (pIgR) in jejunum and lower mRNA expression of IL-1β in jejunum and iNOS, TNF-α in spleen. Furthermore, adequate or excess VK3 significantly increased plasma IgG content, the CAT, T-SOD and total antioxidant capacity activities, up-regulated the mRNA expression of pIgR, Nrf2, SOD1 and CAT in jejunum and down-regulated the mRNA expression of iNOS and TNF-α in spleen. In conclusion, dietary addition of adequate VA (7000 IU/kg) and VK3 (2.0 mg/kg) improved the immune function and intestine antioxidant capacity of aged laying hens and excess levels did not exhibit superior effects.

The Effect of Azadirachta indica leaves extract on Transforming Growth Factor-β and Tumor Necrosis Factor-α in a Plasmodium berghei infected Mice model

Malaria is a health problem for the world's population and is predominantly located in tropical and subtropical areas. The three countries with the most malaria cases are India (58%), followed by Indonesia (20%), then Myanmar (16%). This study aims to determine the effect of neem leaf extract on increasing TGF-β expression and decreasing TNF-α expression in mice infected with Plasmodium berghei. In this study there were four groups, namely Treatment 1 (in Plasmodium berghei infection without therapy). Treatment 2 (in Plasmodium berghei infection and treated with Azadirachta indica leaf extract at a dose of 0.25 mg / g BW). Treatment 3 = (in Plasmodium berghei infection and therapy with Azadirachta indica leaves at a dose of 0.5 mg / g BW). Treatment 4 = (in Plasmodium berghei infection and treated with Azadirachta indica leaves at a dose of 1 mg / g BW). TGF-β examination by elisa method and TNF-α by immunohistochemistry. Data analysis using SEM (Structural Equation Modeling) The results of treatment 1 and 2 showed a decrease in plasma TGF-β expression (t = 1.13; tcount = 1.93; ≥ttabel = 1.96) and spleen (tcount = 1.53; tcount = 1.45; ≥ttabel = 1.96) but there was an increase in spleen TNF-α expression (tcount = 1.77; tcount = 1.00; ≥ttabel = 1.96). Groups 3 and 4 showed an increase in plasma TGF-β expression (tcount = 5.13; tcount = 2.42; ≥ttable = 1.96) and spleen (tcount = 2.00; tcount = 1.97; ≥ttabel = 1.96) but there was a decrease in spleen TNF-α expression (tcount = 2.03; tcount = 2.11; ≥ttabel = 1.96). Conclusion: Azadirachta indica leaf therapy can increase TGF-β expression and decrease TNF-α expression in the spleen.&#x0D; Keywords: Azadirachta indica ethanol extract, transforming growth factor- β, tumor necrosis factor-α

Correlation between elevated inflammatory cytokines of spleen and spleen index in acute spinal cord injury

BackgroundSpinal cord injury (SCI) is a devastating disorder. After SCI, it initiates a robust immune response. Considering the spleen is one of the most important immune organs, the present study further characterizes the inflammatory cytokine profile of spleen in acute SCI. MethodsAdult rats were divided into sham and SCI groups (n = 36). SCI was produced at the T3 vertebral level. The whole blood and spleen was collected at 6, 24, 48, 72, 120, and 168 h after SCI. The levels of the inflammatory factors (IL-1β, IL-6, IL-10, TNF-α, and TGF-β) in spleen and serum were measured with an ELISA kit. ResultsThe results showed significantly elevated levels of IL-1β, IL-6, IL-10 and TNF-α in spleen compared with control group levels. Inflammatory cytokine levels of spleen correlated negatively with spleen index. ConclusionIt was found that inflammatory cytokines in spleen showed dynamic responses to SCI, which suggest their specificity change of spleen caused by SCI. These results suggest that a possible involvement of spleen in the initiation of the inflammatory response after SCI.

UhpA in Edwardsiella piscicida decreases the pathogenicity and the capability of inducing cytokine response in zebrafish

Edwardsiella piscicida (E. piscicida) is one of the main pathogens of fish, which could invade the host through the gut. Glucose 6-phosphate (Glu6P) within the gut provides environmental stresses that affect the pathogenicity of bacteria. Here we focus on a novel two-component chemical signal transduction system, named UhpB/UhpA in E. piscicida, including the key component hexose phosphate transport system regulatory protein (UhpA) coded by the uhpA gene. This study will elucidate the functions of the uhpA gene in the pathogenicity of E. piscicida and the immune response in zebrafish when infected with E. piscicida. The results showed that the wild type strain of E. piscicida EIB202 demonstrated significant increases in growth compared to the mutant strain ΔuhpA with or without 20 mM Glu6P (P < 0.05). The LD50 of E. piscicida △uhpA strain (2 × 104 CFU/fish) for zebrafish was significantly lower than the wild-type strain (1 × 105 CFU/fish), which suggested the uhpA gene deletion could increase its virulence. Besides, fish infected with ΔuhpA showed significantly higher (p < 0.05) gene expression of IL-1β and TGF-β in spleen than fish infected with EIB202 at 6 h, 12 h, 24 h, and 48 h after infection, TNF-α in spleen of fish infected with ΔuhpA showed significantly higher (p < 0.05) than fish infected with EIB202 at 24 h, 48 h, and 72 h after infection, and IFN-γ in spleen of fish infected with ΔuhpA showed significantly higher (p < 0.05) than fish infected with EIB202 at 12 h, 24 h and 72 h after infection. In summary, these results suggest that the uhpA gene deletion in E. piscicida affects Glu6P usage; most important, which could enhance the pathogenicity of E. piscicida in zebrafish, particularly increase the induction of the gene expression of IL-1β, TNF-α, IFN-γ and TGF-β in the spleens of zebrafish after infection.

The evaluation of growth performance, blood health, oxidative status and immune-related gene expression in Nile tilapia (Oreochromis niloticus) fed dietary nanoselenium spheres produced by lactic acid bacteria

The present study was conducted to investigate the effects of lactic acid bacteria-produced nanoselenium spheres (LAB-Se) on the growth performance, blood health, oxidative status and immune-related gene expression in Nile tilapia (initial weight, 14.03 ± 0.04 g). LAB-Se was incorporated into the basal diet at 0.5, 1, 1.5 and 2 mg/kg of diet and fed to the fish for 8 weeks. The results revealed significantly improved final body weights, weight gain, specific growth rates and feed efficiency ratios in fish fed varying levels of LAB-Se (quadratic, P = 0.002, P = 0.002, P = 0.002, and P = 0.04, respectively). The blood haematology and biochemistry parameters of the fish fed varying levels of LAB-Se showed normal values with nonsignificant (P > 0.05) differences, indicating the non-toxic effect of LAB-Se. Additionally, dietary LAB-Se had significant influences on blood total protein and lysozyme and phagocytic activities in tilapia in a dose-dependent manner (quadratic, P = 0.04, P = 0.02, and P = 0.001, respectively). Dietary LAB-Se significantly increased SOD and CAT enzyme activities and decreased MDA levels (quadratic, P = 0.001, P = 0.03, and P = 0.007, respectively); GPX was not significantly affected by LAB-Se inclusion the diets (P > 0.05). Liver and spleen TNF-α expression was significantly upregulated in the fish fed LAB-Se (quadratic, P = 0.007 and P = 0.009, respectively). The expression of liver IL-1β was also upregulated significantly in the fish fed LAB-Se (quadratic, P = 0.005), while spleen IL-1β was not significantly affected by LAB-Se (P > 0.05). Thus, LAB-Se at 1 to 2 mg/kg can be effectively supplemented in tilapia diets to improve growth, oxidative status and immune-related gene expression.

Synergistic Effects of Selenium Nanoparticles and Vitamin E on Growth, Immune-Related Gene Expression, and Regulation of Antioxidant Status of Nile Tilapia (Oreochromis niloticus)

The present study was conducted to investigate the effects of nano-selenium (Nano Se) or/and vitamin E (VE) on growth performance, blood health, intestinal histomorphology, oxidative status, and immune-related gene expression of Nile tilapia. Nano Se or/and VE at a rate of 0, 1 mg Nano Se/kg, 100 mg VE/kg, and 1 mg Nano Se/kg + 100 mg VE diet were fed to fish for 8 weeks. FBW was significantly (P < 0.05) increased in fish fed with Nano Se and VE, while fish fed with Nano Se or Nano Se and VE diets displayed significantly (P < 0.05) higher WG and SGR than the other groups. The lowest FCR was significantly (P < 0.05) detected in fish fed with Nano Se and VE, while the highest value was observed in fish VE diet. The intestinal morphometry (villi length and width) of fish fed with Nano Se or/and VE reported significantly (P < 0.05) the highest values with high number of goblet cells. Blood hematology and biochemistry parameters of fish fed with Nano Se or/and VE showed normal values with insignificant differences except for the blood total protein increased in fish fed with Nano Se or/and VE (P < 0.05). Dietary Nano Se or Nano Se and VE significantly (P < 0.05) increased the GPX, SOD, CAT, NBT, lysozyme, and phagocytosis values with decreased MDA. Liver and spleen TNF-α and IL-1β expressions were significantly (P < 0.05) upregulated in fish fed on Nano Se or Nano Se and VE. Thus, Nano Se or/and VE can be used effectively in tilapia diets for improving the growth, intestinal health, blood health, oxidative status, and immune-related gene expression.

Central serotonin prevents hypotension and hypothermia and reduces plasma and spleen cytokine levels during systemic inflammation

An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280–350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E2 levels in the AVPO at 75 min and 300 min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE2 levels in SI. Intracerebroventricular (icv) administration of 5-HT 30 min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-α, IL-1β, IL-6, and IL-10 and spleen TNF-α and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icv prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway.

Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus.

Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation.

Evaluation of molecular changes of distal organs after small bowel transplantation.

The ischemia and reperfusion of a jejunal graft during transplantation triggers the stress of endoplasmic reticulum thus inducing the synthesis of pro-inflammatory cytokines. Spreading of these signals stimulate immunological reactions in distal tissues, i.e. lung, liver and spleen. The aim of this study was to detect the molecular changes in liver and spleen induced by transplanted jejunal graft with one or six hours of reperfusion (group Tx1 and Tx6). Analysis of gene expression changes of inflammatory mediators (TNF-alpha, IL-10) and specific chaperones (Gadd153, Grp78) derived from endoplasmic reticulum (ER) was done and compared to control group. The qRT-PCR method was used for amplification of the specific genes. The levels of corresponding proteins were detected by Western blot with immunodetection. Protein TNF-alpha was in liver tissue significantly overexpressed in the experimental group Tx1 by 48 % (p<0.001). In the group Tx6 we found decreased levels of the same protein to the level of controls. However, the protein concentrations of TNF-alpha in spleen showed increased levels in group Tx1 by 31 % (p<0.001) but even higher levels in the group Tx6 by 115 % (p<0.001) in comparing to controls. Our data demonstrated that the spleen is more sensitive to post-transplantation inflammation than liver, with consequent stress of ER potentially inducing apoptosis and failure of basic functions of lymphoid tissue.

Silencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis.

MiR-150 regulates maturation and differentiation of T cells but how it functions in multiple sclerosis (MS) is unclear. In miR-150 knockout (KO) mice, we examined the effect of miR-150 deletion on disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. After deleting miR-150, EAE disease severity was reduced according to clinical score. Histological staining and MBP immunofluorescence staining revealed that miR-150 deletion limited the extent of inflammatory demyelination and axonal damage in the spinal cord. Flow cytometry showed that CD3+, CD4+, and CD8+ T cells were increased in WT-EAE mice, but miR-150 deletion significantly reversed EAE-mediated up-regulation of CD3+, CD4+, and CD8+ T cells and down-regulation of CD19+ B cells. In addition, miR-150 deletion reduced the mRNA expression of IL-1β, IL-6, IL-17, and TNF-α in spleen and spinal cord after EAE induction. Thus, miR-150 deletion reduces EAE severity and demyelination, probably through inhibiting the activated immune response and the inflammation in the central nervous system.

The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria

According to the WHO, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. Therefore new antimalarials capable of limiting organ damage are still required. We show that systemic and lung adenovirus (Ad)-mediated over-expression of trappin-2 (T-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing Plasmodium berghei ANKA (PbANKA) strain. Systemically, T-2 reduced PbANKA sequestration in spleen, lung, liver and brain, associated with a decrease in pro-inflammatory cytokines (eg TNF-α in spleen and lung) and an increase in IL-10 production in the lung. Similarly, local lung instillation of Ad-T-2 resulted in a reduced organ parasite sequestration and a shift towards an anti-inflammatory/repair response, potentially implicating monocytes in the protective phenotype. Relatedly, we demonstrated in vitro that human monocytes incubated with Plasmodium falciparum-infected red blood cells (Pf-iRBCs) and IgGs from hyper-immune African human sera produced T-2 and that the latter colocalized with merozoites and inhibited Pf multiplication. This array of data argues for the first time for the potential therapeutic usefulness of this host defense peptide in human malaria patients, with the aim to limit acute lung injury and respiratory distress syndrom often observed during malaria episodes.

Pathological damage and immunomodulatory effects of zebrafish exposed to microcystin-LR

Cyanobacterial blooms caused by water eutrophication have become a worldwide problem. Microcystins (MCs), especially microcystin-LR (MC-LR), released during cyanobacterial blooms exert great toxicity on fish and even lead to massive death. The present study mainly investigated the pathological damage and immune response of spleen, gut and gill in zebrafish exposed to MC-LR. Fish were exposed to 0, 1, 5 and 20 μg/L of MC-LR for 30 d. In zebrafish exposed to 5 and 20 μg/L MC-LR, edematous mitochondria, deformation of the nucleus and compaction of chromatin were observed in lymphocyte of spleen; frayed gut villi, exfoliation of epithelial cells and widespread cell lyses were observed in intestines; hyperemia in gill lamellae, epithelial tissue edema and uplift and lamellar fusion were observed in gill. Varied changed gene expression was observed in spleen, intestine and gill of zebrafish. The transcriptional levels of IFN-1 and IL-8 in spleen significantly up-regulated in 20 μg/L group, and the transcription of IL-1β and TNFα in spleen increased in 1 μg/L MC-LR treated fish. In addition, the mRNA levels of IFN-1, IL-1β, IL-8, TGF-β and TNF-α dramatically increased in intestine and gill in all MC-LR treated groups. The present studies indicated that MC-LR exposure caused marked pathological damage, however, fish could adjust actively the expression of innate immune-related genes to resist the tissue damage. Our findings provided strong evidence of the recovery potential of fish exposed to microcystins.

Effects of Hyriopsis cumingii Polysaccharides on Mice Immunologic Receptor, Transcription Factor, and Cytokine.

To discuss the molecular mechanism of immunoenhancing activities of Hyriopsis cumingii polysaccharides (HCPS), effects of HCPS on mice immunologic receptors (toll-like receptors-4 [TLR-4] and mannose receptor-1 [MR-1]), transcription factor (nuclear factor kappa-B [NF-κB]), and cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) were evaluated by cell model in vitro and cyclophosphamide-induced immunosuppression animal model in vivo. Results showed that HCPS could promote the mRNA synthesis of TLR-4, MR-1, IL-6, and TNF-α in spleen, and the gene expression of TLR-4, MR-1, NF-κB, IL-6, and TNF-α in spleen and serum in a dose-dependent manner. Crude HCPS and its purified fractions (HCPS-1, HCPS-2, and HCPS-3) could strengthen peritoneal macrophage expressing MR-1 and NF-κB in a dose-dependent manner. In addition, HCPS-3 showed stronger promotions on MR-1 and NF-κB than crude HCPS, HCPS-1, and HCPS-2. It suggested that HCPS-stimulated immunostrengthening was mediated, at least in part, by TLR-4/NF-κB/IL-6 and TLR-4/NF-κB/ TNF-α signaling pathways. MR-1, IL-6, and TNF-α might be 3 of the immune regulators mediating immunity and homeostasis when HCPS performed immunoenhancing activities.

가미계작지모탕(加味桂芍知母湯) 주정 추출물이 류마티스 관절염 인자에 미치는 영향

ABSTRACT Objectives : The purpose of this study is to prove the effect of Gamikyejakjimo-tang (jiāweiguishaozhīm-tāng, GK) on rheumatoid arthritis.Methods : We checked viability and measured production of IL-1β, IL-6, IL-17, TNF-α in RAW 264.7 cell after treat by GK. Then we measured rheumatoid arthritis index score of DBA/1 mice with rheumatoid arthritis induced by CIA after GK oral administration, checked IL-1β, IL-6, IL-17, TNF-α and hs-CRP tests in serum. Also we were observed mRNA expression of IL-1β, IL-6, IL-17 and TNF-α in spleen by RT-PCR.Results : GK showed cell viability of 100% or higher in all concentration in RAW 264.7 cells. GK inhibited LPS-induced productions of rheumatoid arthritis mediators cytok ine in RAW 264.7cells. GK treated group showed improvement from rheumatoid arthritis at decreased the i ndex score. Also, GK treated group decreased level in serum of IL-1b, IL-6, IL-17, TNF-a and hs-CRP tests by 31%, 35%, 20%, 57% and 58% respectively. Finally, GK treated group showed decrease expression of IL-1β, IL-6, IL-17 and TNF-α mRNA in spleen by 46%, 51%, 25% and 42% respectively.Conclusions : In this study, in-vitro and in-vivo results observed rheumatoid arthritis factors cytokine of IL-1β, IL-6, IL-17 and TNF-α decrease in RAW 264.7 cells, serum, mRNA expression. Also, GK showed decrease of inflammation figure in hs-CRP tests depending on effect of r heumatoid arthritis. Thus, these results can used as a effective drug of GK for rheumatoid arthritis.Key words : Cytokine, hs-CRP, Gamikyejakjimo-tang, mRNA, Rheumatoid arthri tis, serum

First evidence of the possible implication of the 11-deoxycorticosterone (DOC) in immune activity of Eurasian perch (Perca fluviatilis, L.): Comparison with cortisol

Cortisol, the main corticosteroid in fish, is frequently described as a modulator of fish immune system. Moreover, 11-deoxycorticosterone (DOC) was shown to bind and transcriptionally activate the mineralocorticoid receptor and may act as a mineralocorticoid in fish. Immune modulations induced by intraperitoneal injections of these two corticosteroids were assessed in Eurasian perch juveniles. Cortisol and DOC were injected at 0.8mgkg−1 and 0.08mgkg−1 body weight respectively. Cortisol increased plasma lysozyme activity 72h post-injection, C-type lysozyme expression in spleen from 1 to 72h post-injection, and favoured blood neutrophils at the expense of a mixture of lymphocytes and thrombocytes. Moreover, 6h after injection, cortisol reduced expression levels of the pro-inflammatory cytokine TNF-α in spleen. DOC had no effects on the immune variables measured in plasma, but increased expression levels of C-type lysozyme and apolipoprotein A1 mRNA in both gills and spleen. Meanwhile, DOC stimulated its putative signalling pathway by increasing expression of mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase-2 in spleen. These results confirmed the role of cortisol as an innate, short term immune stimulator. For the first time, DOC is described as a possible immune stimulator in fish.