Levels Of Related Cytokines Research Articles

Th17/Treg imbalance is associated with reduced indoleamine 2,3 dioxygenase activity in childhood allergic asthma

BackgroundThe differentiation of CD4+ lymphocytes Th17/regulatory T cells (Treg) and indoleamine 2,3-dioxygenase (IDO) is associated with the pathogenesis of allergic asthma. Basic research has shown that IDO is likely a “switch” of the transition from Th17 cells to Tregs under certain conditions. However, no relevant clinical studies have been reported on the association between IDO activity and Th17/Treg imbalance in children with allergic asthma. The goal of this study was to test whether indoleamine 2,3 dioxygenase (IDO) participates in the pathogenesis of pediatric allergic asthma by influencing Th17/regulatory T cell (Treg) differentiation and related cytokines.MethodsThirty-three children with allergic asthma and 33 healthy children were selected. The subjects were evaluated via a pulmonary function test, a skin prick test, and an eosinophil count. Peripheral blood was collected to measure Th17/Treg percentages and related cytokine levels. Blood and induced sputum were obtained to measure the IDO level.ResultsCompared with the control group, the patient group had an obvious Th17/Treg imbalance; their IDO levels were significantly lower, their IL-17 and IL-6 levels were markedly higher, and their IL-10 and TGF-β levels were markedly lower than those of the control group. The IDO levels in both blood and induced sputum were negatively correlated with the Th17/Treg ratio.ConclusionsA significant correlation was observed between IDO activity and Th17/Treg imbalance in children with allergic asthma. IDO may upregulate Treg numbers by stimulating IL-10 production and inhibiting IL-6 expression. Therefore, IDO may be a molecular switch that leads to the conversion of Th17 cells to Tregs, thus playing a potentially protective role in the pathogenesis of asthma.Trial registration This study was approved by the Chinese Clinical Trial Registry with registration number ChiCTR-COC-15006080 and was reviewed and approved by the Ethics Committee of Southwest Hospital. The name of registration: The effect of indoleamine 2,3 dioxygenase (IDO) on Regulation of Th17/Treg Differentiation in Childhood Asthma. Date of registration: 14/03/2015. URL of trial registry record: http://www.chictr.org.cn

Inhibition of GSK3β and RIP1K Attenuates Glial Scar Formation Induced by Ischemic Stroke via Reduction of Inflammatory Cytokine Production.

In the chronic phase following ischemic stroke, glial scars can prevent axonal regeneration and the intensification of inflammation. The protective effect of inhibition of glycogen synthase kinase-3β (GSK3β) or receptor-interacting protein 1 kinase (RIP1K) on ischemic stroke has been previously reported. The current study examined the effects of RIP1K and GSK3β on ischemic stroke-induced glial scar formation. To investigate this, we used an in vivo model of ischemic stroke based on middle cerebral artery occlusion for 90 min followed by reperfusion for 7 d, and an in vitro model in primary cultured astrocytes involving oxygen and glucose deprivation for 6 h followed by reoxygenation for 24 h. Both in vivo and in vitro, we found that SB216763, a GSK3β inhibitor, and necrostatin-1 (Nec-1), a RIP1K inhibitor, decreased levels of glial scar markers, including glial fibrillary acidic protein (GFAP), neurocan, and phosphacan. SB216763 and Nec-1 also decreased levels of inflammatory related cytokines, including interleukin-6 (IL-6), interleukin-1 β (IL-1β), and tumor necrosis factor-α (TNF-α). However, only Nec-1 increased the level of interleukin-1 receptor antagonist. Concurrent neutralization of TNF-α, IL-1β, and IL-6 with their antibodies provided better reduction in oxygen and glucose deprivation-induced increases in scar markers than obtained with separate use of each antibody. Further investigations showed that SB216763 reduced the levels of necroptosis-related proteins, including RIP1K, p-RIP1K, RIP3K, p-RIP3K, mixed lineage kinase domain-like protein (MLKL), and p-MLKL, while Nec-1 decreased the expression of p-GSK3β. Compared with Nec-1 (10 μM) and SB216763 (1 μM) alone, Nec-1 and SB216763 in combination reduced levels of GFAP, neurocan, and inflammatory-related cytokines. In conclusion, inhibition of GSK3β or RIP1K reduced glial scar formation induced by ischemic stroke. The underlying mechanisms might be at least, partially related to reducing levels of inflammatory-related cytokines and to blocking an interaction between GSK3β- and RIP1K-mediated pathways.

Immunological effects of anti-coagulant unfractionated heparin in pregnant Chinese women with cryptic recurrent miscarriages.

Anti-coagulant unfractionated heparin of low molecular weight (ACUHlmw) therapy is popularly practised in the therapy of recurrent miscarriages (RMC) due to its anti-coagulant properties. However, several in vitro investigations have hypothesized about the possible immunological effects of ACUHlmw. We examined pregnant women with cryptic RMC (cRMC) to determine whether ACUHlmw could regulate the immune reaction in vivo during their pregnancy. In this study, a total of 51 women were subjected to tinzaparin and 48 patients were considered as control women on the basis of an open single-centre randomized controlled trial. During different fertilization weeks (FW) 7, 19, 29, and 35 plasma samples were acquired for eleven chemokine and cytokine levels and then investigated by multiplex bead technology and selected to portray T-helper subset-related immunity. We did not find any difference in chemokine C-C motif ligand-2, -17, -22, chemokine C-X-C motif ligand-1, -8, -12, -13 or cytokine interleukin-6 when a mixed linear model test was carried out on ACUHlmw in both the study and control women. However, differences were observed in the mixed linear model test on ACUHlmw in both the study and control women during pregnancy of the Th1/Th17 related chemokine C-X-C motif ligand-10 (p = 0.01), -11 (p < 0.001) and chemokine C-C motif ligand-20 (p = 0.04) respectively. A positive outcome of ACUHlmw therapy in vivo was observed, thus establishing its potential proinflammatory effect. During 2nd and 3rd trimesters, the observed harmonious enlargement in Th1/Th17 related chemokine and cytokine levels does not recommend a fruitful immunological impact of ACUHlmw therapy in vivo.

Anthocyanin-Containing Purple Potatoes Ameliorate DSS-Induced Colitis in Mice

Abstract Objectives Ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD), is on the rise worldwide. Approximately 3 million people suffer from IBD in the US alone, but the current therapeutic options (e.g., corticosteroids) come with adverse side effects including reduced ability to fight infections. Thus, there is a critical need for developing effective, safe and evidence-based food products with anti-inflammatory activity. This study aimed to evaluate the anti-inflammatory potential of purple-fleshed potato anthocyanins using a dextran sodium sulfate (DSS) murine model of colitis. Methods Four weeks old male C57BL/6 mice were randomly assigned to control (AIN-93 G diet), P15 (15% purple-fleshed potato) and P25 (25% purple-fleshed potato) diets for eight weeks. Colitis was induced by 2% DSS administration in drinking water for six days. Intestinal permeability was measured using FITC-dextran. Serum and colonic myeloperoxidase (MPO) levels were measured using ELISA and hexadecyltrimethylammonium bromide method, respectively. Flagellin was quantified using human embryonic kidney (HEK)-Blue-mTLR5 cells. RT-PCR was used to analyze the relative gene expression levels of cytokines and pathogenic bacteria abundance. Results 1) Purple- fleshed potato supplementation suppressed (P ≤ 0.05) the DSS-induced reduction in body weight and colon length as well as the increase in spleen and liver weight. 2) P25 alone suppressed (P ≤ 0.05) the elevation in the intestinal permeability and serum MPO levels in DSS-exposed mice. 3) The colonic mRNA expression levels of pro-inflammatory cytokines IL-6, IL-17 and TNF-α were attenuated in mice consuming P25 diet. 4) However, both purple potato diets suppressed the relative abundance of specific pathogenic bacteria such as Enterobacteriaceae and pks + E. coli. However, flagellin levels were significantly (P ≤ 0.05) lower in mice consuming the P25 diet alone. Conclusions Purple-fleshed potato diet consumption dose-dependently ameliorated the DSS-induced elevation in gut permeability, oxidative stress and inflammation and pathogenic gut bacteria. Collectively, our study results suggest that purple-fleshed potatoes have the potential to be used as a functional food in the amelioration of UC symptoms. Funding Sources USDA-NIFA awards 2016-67,017-29,285 and 2019-67,017-29,258.

Role of Gut Microbiota in Anti-Colitic Effects of Color-Fleshed Potatoes

Abstract Objectives The prevalence of ulcerative colitis (UC), a chronic inflammatory bowel disease, is on the rise with ∼700,000 patients in the US alone in 2018. Gut bacterial dysbiosis plays an important role in ulcerative colitis. We have recently shown that anthocyanin-containing potatoes exert anti-inflammatory activity in colitic mice. However, no information is available on whether gut bacteria play a role in the anti-colitic activity of color-fleshed potatoes. This study examined the anti-colitic activity of red/purple-fleshed potatoes in mice with intact and antibiotic-ablated microbiome. Methods We used DSS-induced murine (C57BL6) colitis model with and without the administration of antibiotics in drinking water for nine weeks. Mice were randomly assigned to the control (AIN-93G diet), DSS (AIN-93G diet), DSS + PP (20% purple potato) and DSS + RP (20% red potato) groups. After eight weeks, mice were treated with 2% DSS in their drinking water for five days to induce colitis. Intestinal permeability was measured using FITC-dextran. Serum myeloperoxidase (MPO) levels were measured using ELISA. RT-PCR was used to analyze the relative gene expression levels of cytokines and bacterial abundance. Results Administration of antibiotics resulted in a 95% reduction in gut bacterial load. Antibiotics administration did not alter food intake, water intake, and weight gain. Antibiotic-treated mice had five times greater cecum weight, a hallmark of germ-free mice, compared to no-antibiotic mice. In antibiotic mice, DSS-induced splenomegaly, elevated gut permeability (serum levels of FITC-dextran), and reduced colon length and weight were more pronounced compared to no antibiotic mice. Purple- or red-fleshed potato supplementation (20% w/w) ameliorated (P ≤ 0.05) DSS-induced reduction in colon length, elevation in permeability, spleen weight and MPO levels in no antibiotic mice only. Moreover, purple-fleshed potato supplementation alone improved the ZO-1 and MUC-2 gene expression levels in no-antibiotic mice, but not in microbiota-ablated mice. Conclusions In summary, these results suggest that purple-fleshed potatoes are more potent compared to red-fleshed potatoes and the gut microbiome is critical for the anti-colitic activity of anthocyanin-containing potatoes. Funding Sources USDA-NIFA awards 2016-67,017-29,285 and 2019-67,017-29,258.

Iron overload regulate the cytokine of mesenchymal stromal cells through ROS/HIF-1α pathway in Myelodysplastic syndromes

Iron overload is a significant feature of myelodysplastic syndromes (MDS) patients due to ineffective hematopoiesis and transfusion dependence. Excess iron results in organ dysfunction through the generation of reactive oxygen species (ROS) which can cause oxidative stress even mutation. Mesenchymal stromal cells (MSCs) are responsible for supporting and regulating hematopoiesis, whether MSCs is involved in the pathogenesis of MDS still need further elucidation. Hypoxia-inducible factors-1 (HIF-1) is an integral signal of inflammation that has been shown to up-regulating in MDS patient. We found that MDS-derived MSC had disorganized clones and increased level of apoptosis (n = 53). Iron transportation-related gene, such as DMT1 and ZIP14, and ROS level were increased in iron overload-MDS-MSC (n = 23). HIF-1a, as a crucial part of HIF-1, was also elevated in iron overload-group and PHD2 involved in the degradation of HIF-1a was reduced. Furthermore, HIF-1 downstream cytokines such IL-6, IL-8, TGF-βand VEGF that were also involved in the pathogenesis of MDS were increased in IO-MDS-MSC. When treated with DFO and NAC for iron chelation and antioxidation, the level of HIF-1a and related cytokines could decrease. We conclude that iron overload regulates the cytokine of mesenchymal stromal cells through ROS/HIF-1α pathway in Myelodysplastic syndromes, result in dysfunction of MSC and damage of microenvironment that may be involved in the pathogenesis of MDS.

Mangiferin ameliorates insulin resistance in a rat model of polycystic ovary syndrome via inhibition of inflammation

Purpose: To examine the effect of mangiferin on insulin resistance (IR) in a rat polycystic ovary syndrome (PCOS) model.Methods: The rat PCOS model was established via subcutaneous injection of 6 mg/kg of dehydroepiandrosterone (DHEA), and mangiferin was orally administered. Body and ovarian weights were recorded. Serum levels of glucose, insulin, and related inflammatory cytokines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay, while the expression levels of key proteins were analyzed by western blotting.Results: DHEA significantly increased ovarian weight and the ratio of ovarian weight/body weight (p &lt;0.001), while mangiferin treatment decreased them (p &lt; 0.001). Mangiferin also lowered DHEA-induced enhancements in serum glucose and insulin levels (p &lt; 0.001). The mRNA and, expression and concentrations of inflammatory cytokines (interleukin-6(IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) were also significantly reduced by mangiferin treatment (p &lt; 0.001). Furthermore, mangiferin suppressed phosphorylation of nuclear factor-kappa B (NF-κB) but increased the phosphorylation of protein kinase B (AKT, p &lt; 0.001).Conclusion: These results reveal that mangiferin not only decreases inflammatory cytokine levels by regulating NF-κB signaling pathway but also ameliorates IR in a rat PCOS model via regulating AKT signaling pathway. Thus, mangiferin is a potential therapeutic strategy for the management of PCOS.&#x0D; Keywords: Polycystic ovary syndrome, Mangiferin, Inflammation, Insulin resistance, NF-κB, AKT

Remifentanil improves myocardial ischemia-reperfusion injury in rats through inhibiting IL-18 signaling pathway.

To explore the protective effect of remifentanil against myocardial ischemia-reperfusion injury (MIRI) in rats and its mechanism. The rat models of IRI were established and randomly divided into 1) sham-operation group (S group), 2) IRI rat model group (M group), 3) low-dose remifentanil group (R-L group), 4) moderate-dose remifentanil group (R-M group), and 5) high-dose remifentanil group (R-H group). The rats in R-L group, R-M group, and R-H group were administrated with remifentanil at 0.4 μg/kg/min, 2 μg/kg/min, and 10 μg/kg/min, respectively. The activity of creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in myocardial cells was detected using the automatic biochemical analyzer, and the apoptosis rate of myocardial cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the messenger ribonucleic acid (mRNA) and protein levels of related cytokines in myocardial cells were determined through quantitative Polymerase Chain Reaction (qPCR) and Western blotting, and the content of interleukin-1β (IL-1Symbol ) and IL-18 in peripheral blood was detected via enzyme-linked immunosorbent assay (ELISA). Remifentanil at different concentrations could protect myocardium from IRI, and remifentanil at 2 μg/kg/min and 10 μg/kg/min could significantly down-regulate the myocardial enzyme indexes in IRI myocardial cells (p<0.01). Besides, remifentanil reduced the mRNA expressions of IL-18, INF-γ, TNF-β, and IL-1β (p<0.01), significantly decreased the protein expression of IL-18, and raised the protein expression of IL-18BP, thereby improving myocardial pathological damage. The protective mechanism of remifentanil on the myocardium of MIRI rats may be related to the inhibition on the IL-18 signaling pathway.

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes

Ganoderma Lucidum Polysaccharides Ameliorates Hepatic Steatosis and Oxidative Stress in db/db Mice via Targeting Nuclear Factor E2 (Erythroid-Derived 2)-Related Factor-2/Heme Oxygenase-1 (HO-1) Pathway.

BackgroundType 2 diabetes mellitus (T2DM) and its comorbidities, including obesity, hypertension, and hyperlipidemia, are commonly associated with non-alcoholic fatty liver disease (NAFLD). Ganoderma lucidum polysaccharide (GDLP) is one of the central bioactive components in Ganoderma lucidum with anti-inflammatory, antioxidant, and hepatoprotective properties. However, the effect and mechanisms of GDLP in hepatic steatosis remain largely unknown. In the present study, we aimed to investigate the function of GDLP in hepatic steatosis and the underlying mechanism.Material/MethodsIn this study, male db/db mice were received with a high-fat diet (HFD) to investigate the effect of GDLP in T2DM-induced hepatic steatosis. The biological characteristics of the hepatic steatosis were evaluated through the detection of clinical indicators, including biochemical parameters, histopathology, and related cytokine levels. Additionally, the protein expression levels of Nrf2 (nuclear factor E2 (erythroid-derived 2)-related factor-2) signaling pathway were investigated by using western blotting and immunohistochemical staining.ResultsThe levels of food/water intake, body weight, fasting blood glucose, plasma lipids, urinary biomarkers, hepatic lipid accumulation, and tumor necrosis factor (TNF)-α were observably decreased in GDLP-treated db/db mice. Additionally, administration of GDLP increased the expression of various antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), whereas it reduced the level of malonaldehyde (MDA). Furthermore, GDLP was significantly promoted protein expression level of Nrf2 and its downstream target gene HO-1 (heme oxygenase-1) while decreased TNF-α expression.ConclusionsThese results indicate that GDLP against T2DM-induced hepatic steatosis, oxidative stress, and inflammation by improving the Nrf2/HO-1 signaling pathway in db/db mice, suggesting the GDLP may serve as an effective strategy for in fatty liver treatment.

Effect of Huai Qi Huang on asthma in rats and the mechanism research

To study the role and mechanism of action of Huai Qi Huang (HQH) in the rat model of asthma. Forty Sprague-Dawley rats were randomly divided into a control group, an asthma model group, a budesonide group, and an HQH group, with 10 rats in each group. A rat model of asthma was established by ovalbumin sensitization and challenge. The budesonide group was given budesonide aerosol 2 mg before each challenge. The HQH group was given HQH 4 g/kg dissolved in water by gavage before each challenge. Hematoxylin and eosin staining was used to observe the pathological changes of lung tissues. The percentage of eosinophils in bronchoalveolar lavage fluid (BALF) was measured. Enzyme-linked immunosorbent assay was used to determine the levels of interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), interferon gamma (INF-γ), and immunoglobulin E (IgE) in BALF. Flow cytometry was used to determine T-helper type 1 (Th1)/T-helper type 2 (Th2) ratio in peripheral blood and the spleen. RT-PCR and Western blot were used to measure the mRNA and protein expression of T-bet and GATA-3 in lung tissue. Compared with the control group, the asthma model group showed significant increases in the degree of airway inflammation, the percentage of eosinophils in BALF, and the levels of IL-3, IL-4, IL-5 and IgE in BALF (P<0.05), however, the asthma model group showed significant reductions in the levels of IL-10 and INF-γ in BALF (P<0.05). The asthma model group had significantly lower percentage of Th1 cells but significantly higher percentage of Th2 cells in peripheral blood and the spleen compared with the control group (P<0.05). The mRNA and protein expression of T-bet in lung tissue was significantly lower, but the mRNA and protein expression of GATA-3 in lung tissue was significantly higher in the asthma group than those in the control group (P<0.05). Both HQH and budesonide significantly improved airway inflammation and the above markers in asthmatic rats (P<0.05), with comparable effects between them. However, there were still significant differences in these indices between the control group and the HQH or budesonide group (P<0.05). HQH can reduce the airway inflammation of asthmatic rats and alleviate the symptoms of asthma, possibly by regulating the levels of related cytokines and Th1/Th2 ratio through the T-bet/GATA-3 pathway.

Acupuncture reduce colonic inflammation by suppressing oxidative stress and endoplasmic reticulum stress in rats with ulcerative colitis

To investigate the effect of manual acupuncture (MA) and electroacupuncture (EA) on histopathological changes, and levels of oxidative-stress related cytokines and key proteins of the endoplasmic reticulum stress (ERS) pathway in ulcerative colitis (UC) rats, so as to reveal their mechanisms underlying improvement of UC. Twenty-eight male SD rats were randomly divided into control, model, EA and MA groups (n＝ 7 rats per group). The UC model was established by enema of mixture solution of 5% 2, 4, 6-trinitrobenzene sulfonic acid (TNBS, 100 mg/kg). Rats of the control group received intra-rectal perfusion of normal saline. After modeling, the left "Quchi"(LI11) and "Zusanli"(ST36) were stimulated with EA (2-4 mA，8 Hz/25 Hz) or MA for 20 min, once every other day for consecutive 2 weeks. The rats in the control and model group were just anesthetized and fixed. At the end of experiments, the colon tissue was collected for observing histopathological changes with H．E. staining. The contents of oxidative stress-related factors as superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (T-AOC) were detected by ELISA, and the expression levels of key proteins of ERS as phosphorylated inhibitor of nuclear factor kappa B kinase α (p-IκBα), phosphorylated p65 (p-p65), glucose regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) by using Western blot. After modeling, the colon tissues showed severe swelling, disordered arrangement of intestinal mucosal cells, hemorrhage with infiltration of inflammatory cell and partial loss of colon villus, which was relatively milder in the EA and MA groups. The colonic lesion score was remarkably increased in the model group in contrast to the control group (P<0.01), and obviously reduced in both EA and MA groups relevant to the model group (P<0.01). The levels of SOD, CAT, GSH and T-AOC were all significantly decreased (P<0.01), and the content of MDA, and expression levels of p-IκBα， p-p65 and GRP78, p-PERK and p-eIF2α proteins were all significantly increased in the model group relevant to the control group (P<0.01). After the treatment, modeling-induced down-regulation of SOD, CAT and GSH in both EA and MA groups, and T-AOC in the EA group, and up-regulation of levels of MDA, p-IκBα， p-p65, GRP78, p-PERK and p-eIF2α in both groups were reversed (P<0.01, P<0.05). Both EA and MA treatment can obviously alleviate colonic inflammation in UC rats via inhibiting oxidative stress and ERS.

ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway.

Diabetic nephropathy (DN) is one of the main causes of renal fibrosis and is associated with high morbidity and mortality. Traditional Chinese Medicine (TCM) therapy has a long history of usage in a clinical setting and its usage is increasing. ErHuang Formula (EHF), a Chinese herbal compound, has been clinically used in treating DN for more than 30 years. However, its mechanism of action is still unknown. This study was conducted to evaluate the effect of EHF on renal fibrosis in a DN rat model and explore its underlying mechanism. The DN rat model was established by high-sugar-fat diet combined with a single intraperitoneal injection of streptozotocin (STZ), and EFH extract (4, 2, 1 g/kg d−1) was administered orally for 8 weeks. The biochemical parameters (blood glucose, weight, Scr, BUN, UA, U-Alb and UAE) were analyzed. The pathological changes in renal tissue were observed by histological staining with H&E and Masson. The effect of EHF on the proliferation of NRK-49F cells was examined by CCK-8 assay and the levels of several inflammation and fibrosis related cytokines (IL-6, TNF-α, TGF-β1, Collagen I/III, MMP2/9) in serum and NRK-49F cell culture supernatants were detected by enzyme-linked immunoassay (ELISA). The mRNA levels of CXCL6, CXCR1, Collagen I/III, MMP2/9 in renal tissue were also measured by quantitative RT-PCR. Furthermore, the protein expression of PCNA, Collagen I/III, MMP2/9, CXCL6, CXCR1, p-STAT3, STAT3 in renal tissue and NRK-49F cells were determined by western blot. EHF improved the abnormal biochemical parameters and ameliorated the abnormal histology and fibrosis of renal tissue in a dose-dependent manner. EHF inhibited NRK-49F proliferation and decreased the expressions of inflammation and fibrosis related factors both in vitro and in vivo. Interestingly, the levels of Collagen I/III, PCNA, MMP2/9 and p-STAT3 were positively correlated with CXCL6. The amelioration of renal fibrosis in DN by EHF is related to CXCL6/JAK/STAT3 signal pathway, which is associated with inflammation and fibrosis of the tissue. These findings may have clinical implications for the treatment of DN.

Catalpol ameliorates Sjögren’s Syndrome by modulating interplay of T and B cells

Catalpol is an active ingredient of Rehmanniae Radix, a medical herb used frequently in treating primary Sjogren’s Syndrome (pSS). However, no study has assessed the therapeutic effects of catalpol in treating Sjogren’s Syndrome. This study aimed to investigate the therapeutic effects of catalpol for pSS by evaluating the water consumption, stimulated salivary flow rates, sialadenitis, T cell subsets and related cytokine levels. Catalpol treated mice had improved stimulated salivary flow rates and water consumption compared to mice from the control group. Catalpol also reduced the lymphocytic infiltration and prevented the formation of ectopic germinal centers. These effects, especially in the catalpol high dose group, were associated with elevated CD4+ CXC-R5+ PD-1+ Foxp3+ T follicular regulatory (Tfr) cells (1.572 % vs 1.118 %, P = 0.0005) and a higher ratio of Tfr cells to T follicular helper (Tfh) cells (2.137 vs 1.541, P = 0.0007). Downregulated levels of IFN-γ and BAFF in serum and submandibular glands were also noted in catalpol treated groups. Our work indicated that catalpol might be a potential drug for treating pSS by regulating the interplay between T and B cells.

Methanolic extracts of Capparis ecuadorica iltis inhibit the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophage cells

Background: Some species of the caper family are known to possess antibacterial, antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties. However, to date, the therapeutic effects of Capparis ecuadorica Iltis (Capparis L.) have not been studied. Objectives: In this study, we investigated the anti-inflammatory activity of a methanolic extract of C. ecuadorica leaves (MCE) in macrophages. Materials and Methods: Anti-inflammatory responses and mechanisms were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after pretreatment with MCE. Results: In the MCE + LPS-treated group, the relative mRNA levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6) were downregulated and protein levels of IL-6 were also decreased as compared to the vehicle + LPS-treated group. Furthermore, the MCE + LPS-treated group showed reduced levels of reactive oxygen species (ROS) production as compared to the vehicle + LPS-treated group; detection of nitrite concentration revealed nitric oxide (NO) to be the reduced ROS. The expression levels of inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2) mRNA and the level of phosphorylation of IκBα were decreased in the MCE + LPS-treated group. In addition, MCE + LPS-treated group showed reduced levels of phosphorylation of MAP kinase in comparison to the vehicle + LPS-treated group. Interestingly, MCE also inhibited other inflammatory mechanisms, namely, endoplasmic reticulum (ER) stress and autophagy. Conclusion: These results indicate that MCE inhibits inflammatory responses through the inhibition of inflammatory cytokines and NO production, iNOS/COX-2 expression and nuclear factor-kappa B (NF-κB) activation, MAPK inhibition, as well as regulation of ER stress and autophagy in LPS-stimulated RAW 264.7 cells.

Impact of simultaneous neutralization of IL-17A and treatment with recombinant IL-2 on Th17-Treg cell population in S.aureus induced septic arthritis

The contribution of Th17 and Treg in the pathogenesis of septic arthritis is well known. The imbalance of Th17/Treg ratio, especially the skewed CD4+ T cell differentiation towards pathogenic Th17 lineage is a major reason that mediates bone damage through one of its prime cytokine member IL-17A. The neutralization of released IL-17A, as well as exogenous administration of IL-2 at a lower dose, was seen to be potent in dampening the inflammatory response in many cases. Interestingly the effect of IL-17A neutralization to limit IL-17 mediated inflammation and induction of Tregs by the administration of IL-2 has not been studied in experimental arthritis. So in this study, we have treated arthritic mice with IL-17A Ab and recombinant mouse IL-2 either alone or in combination at 3, 9 and 15 days post-infection. We have found a marked decrease in Th17 cell population and their related pro-inflammatory cytokine levels at 15DPI in arthritic mice after IL-17 neutralization. An increased Treg cell population was also observed in mice after application of rIL-2 with a significantly heightened TGF-β level in serum and synovial joints compared to the untreated one. However, in the case of combination therapy of IL-17A Ab and rIL-2 we have observed a beneficial effect in ameliorating the disease outcome as the arthritic index was decreased maximally at 15DPI with a significant reduction of arthritis compared to individual treatment. Overall the inflammatory microenvironment was counterbalanced most effectively in combination treatment by lowering the Th17/Treg ratio and their related cytokines that resulted in reducing the immunopathogenesis of the destructive arthritis.

Pronounced immunological abnormalities in unmedicated first episode as compared to chronic schizophrenia patients

There is major evidence for the involvement of immunological processes in the pathophysiology of schizophrenia. Especially alterations of T-cell function and activation of the inflammatory response system appear to be linked to schizophrenia. A mild chronic inflammation process has been proposed and repeated findings of altered serum cytokine levels led to the hypothesis of a TH2 shift or cytokine imbalance in schizophrenia. We investigated serum levels of TH1 and TH2 related cytokines and immune markers in 25 patients suffering an acute schizophrenic episode (all unmedicated, 22 neuroleptica-naïve) at different stages of disorder (18 first episode, FEP; 7 recurrent episode, REP) compared to 25 age and sex matched healthy controls.In patients, we found an increase of the TH2 system cytokine IL-13 (p = 0.039) and a decrease of the TH1 system markers sICAM-1 (p = 0.011) and sIL-2R (p = 0.063, n. s.). Elevation of the pro-inflammatory cytokine IL-6 was not significant (p = 0.052). The effect of sIL-2R decrease was greater in the FEP subgroup (p = 0.01) of patients. We found no group differences in the other investigated immune markers: IL-4, IL-8, TNF-alpha, and Interferon-gamma, in which most readings were below the lower detection limit of the respective assay.Our findings support the notion of a TH1/TH2 imbalance particularly in the acute manifestation phase of schizophrenia. In the long run, this may lead to the identification of cytokine patterns that are applicable as trait or state markers, may be helpful in making or ensuring diagnosis or in monitoring therapy.

Biological depletion of neutrophils attenuates pro-inflammatory markers and the development of the psoriatic phenotype in a murine model of psoriasis

Although neutrophils are considered a histologic hallmark of psoriasis, their pathophysiologic role in psoriasis remains unclear. We characterized the effects of neutrophil depletion via injection of monoclonal antibody 1A8 on the development of imiquimod (IMQ)-induced psoriatic lesions in a murine model. Lesions were followed with photographs and histologic analysis, revealing reduced psoriasiform scale and epidermal hyperplasia in neutrophil-depleted. ELISA and flow cytometry were used to determine relative levels of cytokines and immune cells. Compared to controls, IMQ-treated neutropenic mice had significantly lower levels of macrophages in tissue samples (P < .05) and displayed significantly lower numbers of CD4+ T-cells (P < .05). Neutropenic animals exhibited lower levels of TNF-α, IFN-γ, and IL-1β than controls (P < .05). These results show that neutropenia reduces the development of psoriasiform skin lesions and substantially decreases infiltration of pro-inflammatory cytokines and immune cells to IMQ-induced cutaneous lesions, suggesting an active role of neutrophils in maintaining inflammation in psoriasis.

Clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis: a retrospective observational study

BackgroundSecondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis.MethodsA four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively.ResultsA total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90.ConclusionsUrinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.

Imbalance of Th22/Treg cells causes microinflammation in uremic patients undergoing hemodialysis.

Background: Regulatory T (Treg) cells are of critical functionality in immune activation and inflammation in uremic patients undergoing hemodialysis (HD). A disruption in balance of Treg cells has potency to elicit infectious disease progression. Here, we examined possible association between ratio imbalance of Th22/Treg cells and microinflammation in uremic patients undergoing HD.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated to allow measurement of the percentage of Th22 cells and Treg cells using flow cytometry. Subsequently, serum levels of related cytokines, interleukin (IL) 22 (IL-22) and IL-10 and inflammatory factors, C-reactive protein (CRP), (TNF-α), IL-6 were determined via enzyme-linked immunosorbent assay (ELISA). Then relationships among dialysis time, microinflammation status (CRP) and dialysis adequacy (immunoreactive parathyroid hormone (iPTH), urea clearance index (Kt/V), β2-MG, serum calcium, and serum phosphorus) were evaluated. Finally, correlation between microinflammation status and dialysis adequacy was analyzed with Pearson’s correlation coefficient.Results: An increased percentage of Th22 and a decreased percentage of Treg cells were evident in uremic patients undergoing HD. Serum levels of IL-22, CRP, TNF-α, and IL-6 were increased, while IL-10 serum level was reduced. An imbalance of Th22/Treg cells was associated with microinflammation status in uremic patients undergoing HD. Furthermore, prolongation of the dialysis time, the microinflammation status and dialysis adequacy were changed. Increased dialysis adequacy was observed to correlate with alleviated microinflammation of uremic patients undergoing HD.Conclusions: Conjointly, an imbalance of Th22/Treg cells may be a potential cause responsible for uremia occurrence, which in turn indicates that uremia could be effectively alleviated by altering the ratio of Th22/Treg cells.