Serum Levels Of MCP-1 Research Articles

Inhibitory effect of polysaccharide of Sargassum weizhouense on PCV2 induced inflammation in mice by suppressing histone acetylation

Seaweeds are excellent source of bioactive compounds and seaweed-derived polysaccharides have demonstrated an array of biological effects. Here, we investigated the effect of polysaccharide of Sargassum weizhouense (PSW) on the inflammatory response in porcine circovirus type 2 (PCV2) infected mice and the underlying mechanism was studied according to the histone acetylation. After PCV2 infection, the levels of TNF-α, IL-1β, IL-6, IL-8, IL-10, MCP-1, COX-1, COX-2 and HAT in both serum and spleen were significantly increased (P <0.05). The mRNA expression of TNF-α, IL-6, IL-10 and NF-κB p65 were elevated in PCV2 infected mice (P <0.05). The HDAC content in both serum and spleen as well the mRNA expression of HDAC1 were greatly decreased (P <0.05). PSW treatment dramatically inhibited the secretions of inflammatory cytokines and HATs, reduced mRNA expression of TNF-α, IL-6, IL-10 and NF-κB p65, but promoted HDAC secretion and mRNA expression of HDAC1 in PCV2-infected mice. The acetylation of both H3 and H4 was significantly up-regulated in PCV2-infected mice, and strongly inhibited by PSW treatment (P <0.01). These results suggested that PCV2 mediate the equilibrium between HATs and HDACs, alternate the histone acetylation and thus DNA packaging, and then activate the transcription of inflammatory cytokines. PSW could inhibit the histone acetylation and the production of inflammatory cytokines, showing excellent potentials in improving the resistance of host against PCV2 infection.

Effects of Desloratadine Citrate Disodium on Serum Immune Function Indices, Inflammatory Factors and Chemokines in Patients with Chronic Urticaria.

To determine the effects of desloratadine citrate disodium on serum immunological function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) in patients with chronic urticaria. An experimental study. Department of Dermatology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China, from January 2017 to January 2018. A total of 128 patients with chronic urticaria were randomly divided into a control group and an observation group, with 64 patients in each group. The patients in the control group were treated with loratadine and those in the observation group were treated with desloratadine citrate disodium. After 4 weeks of treatment, the serum levels of immune function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) were determined. After 4 weeks of treatment, the levels of serum IgE, IL-4, IL-17, IL-33, MCP-1, RANTES and Eotaxin in the observation group were lower than those in the control group (all p<0.001). The levels of serum C3 and C4 in the observation group were higher than those in the control group (both p<0.001). Desloratadine citrate disodium can effectively reduce the severity of chronic urticaria, and its therapeutic mechanism may be related to balancing Th1/Th2 cell function, regulating inflammatory mediators and inhibiting the action of chemokines.

Novel function of PiT1/SLC20A1 in LPS-related inflammation and wound healing

PiT1/SLC20A1 is an inorganic phosphate transporter with additional functions including the regulation of TNFα-induced apoptosis, erythropoiesis, cell proliferation and insulin signaling. Recent data suggest a relationship between PiT1 and NF-κB-dependent inflammation: (i) Pit1 mRNA is up-regulated in the context of NF-κB pathway activation; (ii) NF-κB target gene transcription is decreased in PiT1-deficient conditions. This led us to investigate the role of PiT1 in lipopolysaccharide (LPS)-induced inflammation. MCP-1 and IL-6 concentrations were impaired in PiT1-deficient bone marrow derived macrophages (BMDMs) upon LPS stimulation. Lower MCP-1 and IL-6 serum levels were observed in Mx1-Cre; Pit1lox/lox mice dosed intraperitoneally with LPS. Lower PiT1 expression correlated with decreased in vitro wound healing and lower reactive oxygen species levels. Reduced IκB degradation and lower p65 nuclear translocation were observed in PiT1-deficient cells stimulated with LPS. Conversely, PiT1 expression was induced in vitro upon LPS stimulation. Addition of an NF-κB inhibitor abolished LPS-induced PiT1 expression. Furthermore, we showed that p65 expression activated Pit1 promoter activity. Finally, ChIP assays demonstrated that p65 directly binds to the mPit1 promoter in response to LPS. These data demonstrate a completely novel function of PiT1 in the response to LPS and provide mechanistic insights into the regulation of PiT1 expression by NF-κB.

Abstract WP534: Cyanidin 3-glucoside and its Metabolites Protect Against Nonalcoholic Fatty Liver Disease: Crosstalk Between Serum Lipids, Inflammatory Cytokines and MAPK/ERK Pathway

Background: Serum lipids and inflammatory cytokines are considered as potential therapeutic targets for nonalcoholic fatty liver disease, which has become the most common chronic liver disease in adolescents. Cyanidin 3-glucoside (C3G) is a natural anthocyanin occurs widely in plants, and has shown potential inhibitory effect on inflammatory cytokines in our previous studies. Methods: First, serum levels of inflammatory cytokines including TNF-α and MCP-1 were measured in 80 adolescents (9-15 years old) selected based on their body mass index and serum levels of lipids. Second, the protective effects of C3G and its metabolites including protocatechuic acid (PCA), phloroglucinaldehyde (PGA), ferulic acid, and vanillic acid on nonalcoholic fatty liver disease were measured in a mouse model in which C57BL/6N mice (n=4 for each group) were fed a normal diet, high fat diet only, or high fat diet containing 0.4% of C3G or the four metabolites for 3 months. Finally, the regulatory effects of C3G and its metabolites on inflammatory pathways were clarified in mouse macrophages. Results: Compared with serum levels of MCP-1 (273.13±16.89 pg/ml, n=16) and TNF-α (26.07±1.36 pg/ml) in normal adolescents, those who were obese with abnormal high serum LDL-c/HDL-c ratio (2.88±0.11) had higher MCP-1 (345.19±11.82 pg/ml, P &lt;0.05) and TNF-α (35.70±1.90 pg/ml, P &lt;0.05) levels. However, no significant change was observed in MCP-1 or TNF-α levels in adolescents who had a lower LDL-c/HDL-c ratio, even though their serum levels of total cholesterol and triacylglycerol were significantly higher ( P &lt;0.05) than normal level. Mice experiments revealed that supplement with C3G, PCA or PGA, but not ferulic acid or vanillic acid, prevented high fat diet-induced obesity and fatty liver with lower serum LDL-c/HDL-c ratio and levels of MCP-1 and TNF-α. Cell signaling analysis indicated that C3G, PCA and PGA suppressed the activation of MAPK pathway, especially, C3G and PGA could directly bind to ERK1/2. Conclusion: The serum LDL-c/HDL-c ratio is closely associated with the inflammatory status in nonalcoholic fatty liver disease, and C3G can suppress the inflammation via MAPK/ERK pathway potentially through its metabolites PCA and PGA.

One-year follow-up of the immune profile in serum and selected sites of generalized and localized aggressive periodontitis

BackgroundThe local and systemic immunological profiles of important inflammatory mediators in the localized (LAgP) and generalized (GAgP) forms of aggressive periodontitis are still unknown, as well as the effect of periodontal therapy on these parameters. The aim of this prospective study was to evaluate clinical and immune responses of patients with AgP undergoing nonsurgical treatment. Material and methodsEighteen patients with GAgP, 10 with LAgP and 10 healthy participants were included in this study. AgP participants were submitted to scaling and root planing plus systemic antibiotics (amoxicillin and metronidazole). At baseline and 1-year follow-up were measured clinical parameters, such as probing depth [PD] and clinical attachment loss [CAL], and the levels of 10 immunological mediators (GM-CSF, M-CSF, MCP-1, ICAM-1, CXCL8, IL-1β, TNF-α, IL-17, IL-4, and IL-10) in the gingival crevicular fluid (GCF) of selected sites [AgP forms: PD ≥ 6 mm or the deepest, bleeding on probing (BoP) and bone loss measured by periapical radiography; healthy individuals: PD ≤ 3 mm, no BoP, no bone loss] and serum. ResultsAfter periodontal treatment both forms of AgP presented a significant reduction of PD and CAL, an increase of GM-CSF, ICAM-1, MCP-1, TNF-α, IL-17, IL-4, and IL-10 in the GCF, as well as of GM-CSF and IL-4 in the serum, and a reduction in the serum concentration of IL-1β. Serum levels of M-CSF, ICAM-1, and MCP-1 remained significantly below those found in healthy individuals in both forms of AgP even after therapy. An increase in the systemic or local levels of MCP-1, ICAM-1 and the anti-inflammatory profile (IL-4, IL-10) was correlated with an improvement in clinical parameters of LAgP patients. Also, a local reduction of IL-1β levels in both forms of AgP was correlated with an increase in the clinical attachment gain. ConclusionNonsurgical periodontal therapy was successful in improving clinical parameters and modulating the immune response in both forms of AgP. However, this therapeutic approach does not seem to affect the deficient level of important serum mediators involved in mechanisms of cell transmigration.

Chinese Herbal Formula Feilin Vaginal Gel Prevents the Cervicitis in Mouse Model.

Cervicitis is a common sexually transmitted disease. In recent years, the abuse of antibiotic in the treatment of cervicitis results in the emergence of antibiotic-resistant bacteria; alternative strategies are needed to be developed. In this research, we investigated the effects of Feilin Vaginal Gel (FVG), a Chinese herbal formula, on the treatment of cervicitis. Two cervicitis models were optimized using BALB/c mouse; one in vitro model was established in HeLa cells. In Chlamydia trachomatis-induced cervicitis model, the high level of bacterial loads, the inflammation in tissue, and the cytokines in serum could be observed. With the administration of FVG, the bacterial loads in cervical mucus and cervix tissue could be significantly inhibited in dose-dependent manners. The pathological injury of cervix and vagina, as well as the levels of IL-2, IL-17, and MCP-1 in serum, could be mitigated by FVG. FVG reduced the number of inclusion induced by C. trachomatis in HeLa cells. In addition, the histological damage in Escherichia coli and Staphylococcus aureus-induced cervicitis model could be reduced by FVG. These results suggest that FVG is capable of treating cervicitis through the inhibition of pathogens and the regulation of host immune responses. FVG may contribute as an alternative agent for the treatment of cervicitis.

N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion.Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia.Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 μg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6–8 in the model.Results: In the gouty arthritis rat model, BHA at a higher dosage (50 μg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1β, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 μg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%.Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.

43: Elevated mid-trimester maternal serum cytokines are associated with spontaneous preterm birth in women undergoing cerclage

To examine the role of maternal serum inflammatory biomarkers in the mid-trimester in women undergoing cerclage and assess the differences in serum cytokines between women destined to deliver preterm versus those who deliver at term after cerclage placement. Prospective cohort study of singleton, non-anomalous pregnancies from 2016-2018 at a single tertiary institution who underwent a history-indicated, ultrasound-indicated (mid-trimester CL <25mm), or exam-indicated (asymptomatic cervical dilation) cerclage <24 weeks. Maternal blood was collected in the perioperative period. A custom magnetic bead Luminex cytokine assay was used to measure serum inflammatory cytokines (IL-1b, IL-6, IL-8, GCSF, MCP-1, TNF-a, MMP-8). Cytokine levels were compared between women with spontaneous preterm birth (SPTB) <37 weeks and those with term births. A statistical cut point was calculated for each cytokine to determine the optimal sensitivity and specificity of the cytokine in SPTB prediction. Women were classified as having a ‘high’ or ‘low’ result for each cytokine based on this cut point. Data were analyzed using t-test, chi2, Cox regression, and Kaplan-Meier curves. 42 women met inclusion criteria; 20 (47.6%) had SPTB and delivered at a median 29.6 (IQR 27.3-34.1) weeks. Samples were collected at a median of 0 (IQR -2 to 20) days after cerclage, at a median 17.6 (IQR 12.9-21.1) weeks’ gestation. Baseline characteristics were similar between SPTB and term births (Table). Maternal serum levels of IL-6, MCP-1, and MMP-8 were higher in women with SPTB (Table). Overall, 10 women (24%) had 0-1 high cytokine results, 15 (35%) had 2 or 3, and 17 (41%) had ³4 high cytokine results. A greater number of high inflammatory cytokines [Hazard Ratio (HR) 3.4, 95% CI 2.0-5.7)] and ultrasound- or exam-indication for cerclage (HR 3.5, 95% CI 1.7-7.4) were associated with earlier delivery GA. Increasing numbers of high cytokine results were associated with preterm delivery (Figure). Presence of ³4 high cytokine results was 75% sensitive and 91% specific for SPTB (AUC 0.84, 95% CI 0.71-0.97; PPV=88%, NPV=80%). Among women who undergo cerclage and lack signs or symptoms of labor or intra-amniotic infection, an elevated maternal serum cytokine profile drawn in the perioperative period is associated with SPTB. Confirmation and refinement of this panel may provide insight into improved selection of patients who may benefit from cervical cerclage.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Modulation of Gut Microbiota by Lonicera caerulea L. Berry Polyphenols in a Mouse Model of Fatty Liver Induced by High Fat Diet.

Polyphenols from the Lonicera caerulea L. berry have shown protective effects on experimental non-alcoholic fatty liver disease (NAFLD) in our previous studies. As endotoxins from gut bacteria are considered to be the major trigger of inflammation in NAFLD, this study aims to clarify the regulatory effects of L. caerulea L. berry polyphenols (LCBP) on gut microbiota in a high fat diet (HFD)-induced mouse model. C57BL/6N mice were fed with a normal diet, HFD, or HFD containing 0.5–1% of LCBP for 45 days. The results revealed that supplementation with LCBP decreased significantly the levels of IL-2, IL-6, MCP-1, and TNF-α in serum, as well as endotoxin levels in both serum and liver in HFD-fed mice. Fecal microbiota characterization by high throughput 16S rRNA gene sequencing revealed that a HFD increased the Firmicutes/Bacteroidetes ratio, and LCBP reduced this ratio by increasing the relative abundance of Bacteroides, Parabacteroides, and another two undefined bacterial genera belonging to the order of Bacteroidales and family of Rikenellaceae, and also by decreasing the relative abundance of six bacterial genera belonging to the phylum Firmicutes, including Staphylococcus, Lactobacillus, Ruminococcus, and Oscillospira. These data demonstrated that LCBP potentially attenuated inflammation in NAFLD through modulation of gut microbiota, especially the ratio of Firmicutes to Bacteroidetes.

Vinpocetine regulates levels of circulating TLRs in Parkinson's disease patients.

The pathogenesis of Parkinson's disease (PD) is complex; it includes mitochondrial dysfunction, oxidative stress, and neuroinflammation. Notably, Toll-like receptors (TLRs) may activate inflammatory or anti-inflammatory responses in Parkinson's disease. Vinpocetine has been tested as an anti-inflammatory in both animal and in vitro research. Thus, it is important to test whether the anti-inflammatory properties of vinpocetine may have a protective effect in PD patients. Eighty-nine Parkinson's disease patients and 42 healthy controls were recruited for this study. All patients were randomly assigned to either the traditional therapy group (T PD group, n = 46) or the vinpocetine group (V PD group, n = 43), in a blinded manner. Both treatments were administered for 14days. Administration of vinpocetine reduced mRNA levels of TLR2/4, as well as protein levels of the downstream signalling molecules, MyD88 and NF-κB; moreover, it lowered the expression levels of serum inflammatory cytokines, TNF-α and MCP-1. Notably, vinpocetine increased TLR3 mRNA levels, as well as protein levels of the downstream signalling molecules TRIF-β and IRF-3, and serum levels of the anti-inflammatory cytokines IL-10 and IL-8. Furthermore, vinpocetine produced a robust increase in the Mini Mental State Examination score, compared to that achieved by using levodopa therapy. Vinpocetine treatment may exhibit anti-inflammatory activity and alleviate cognitive impairment.

OR-033 Alterations in Inflammatory Markers and Hepatic Lipid Accumulation following Dietary and Exercise Intervention of Obese Rats

Objective This study aimed to investigate the effects of diet and different exercise training: High Intensity Interval Training (HIIT) and Continuous Training (CT) on body mass gain, serum inflammatory markers and hepatic lipid accumulation of obese rats.&#x0D; Methods Male Sprague-Dawley rats were fed with a normal standard diet (N) or a high fat diet (H; 45% kcal as fat) for eight weeks without exercise stimuli. Obese rats were defined as increased at least 20% body weight than normal diet rats. After this period, N rats were continue fed with a normal diet (N), and half of obese rats were fed with a normal diet (ON), while the other half were continue fed with a high-fat diet (OH). Each diet type group was then divided into three subgroups, control (NC, ONC, OHC groups), High Intensity Interval training (NHI, ONHI, OHHI groups) and Continuous Training (NCT, ONCT, OHCT groups) (n=10). The interval and continuous straining consisted of a swimming exercise performed over eight weeks. Body weight, serum inflammatory markers, plasma and liver lipid concentrations were measured.&#x0D; Results Obese high fat diet rats showed greater body mass gain, visceral adipose tissue (VAT) mass, serum low density lipoprotein (LDL), triglycerides (TG), total cholesterol (TC), and serum inflammatory markers（MCP-1、IL-1β、TNF-α）in values than normal diet rats (OHC versus NC). In contrast, for the obese normal diet rats, no significantly difference was observed compared with normal diet rats on VAT weight, serum lipids, inflammatory markers except MCP-1 (ONC versus NC). On the other hand, the trained groups of obese high fat diet rats showed lower values of body and VAT weight, serum lipids, inflammatory markers levels compared with the OHC group and CT showed more remarkable effect than HIIT except on VAT weight, serum IL-1β levels (OHHI versus OHC and OHCT versus OHC). However, the significantly positive effect of CT on obese normal diet rats was only observed on serum TG, LDL and MCP-1 levels (ONCT versus ONC). In addition, compared to normal rats, hepatic wet weight (HWW)，liver triglycerides (TG) in the OHC group presented obvious high level (OHC versus NC), no differences were exhibited between ONC and NC groups. Interestingly, HIIT but not CT significantly deceased liver TG content compared with OHC group (OHHI versus OHC and OHCT versus OHC), which consistent with liver oil red O stain images as well as higher hepatic CPT-1 level.&#x0D; Conclusions Both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed obese rats, HIIT displayed more positive effect on hepatic lipid accumulation. Additionally, diet and exercise was more effective than exercise alone in reducing body weight, VAT mass, serum inflammatory and liver TG content.

Serum level of IL-8 is associated with reversion of QuantiFERON-TB gold in-tube tests

Frequent reversion has been commonly observed in serial QuantiFERON-TB Gold In-Tube (QFT) tests, which limited its accuracy in defining the status of Mycobacterium tuberculosis (MTB) infection. Serum cytokine profiles might provide additional information to clarify the infection status. Based on a population-based cohort study aiming to track MTB infection acquisition and disease development, serum profiles of 12 cytokines were determined by bead-based multiplex assays in parallel with QFT and tuberculin skin tests (TST) to explore potential relation between serum cytokines and MTB infection status. Totally, 309 subjects got QFT conversion in one year (2013-2014) and 46.92% (145/309) of them got reversion in 2015. The study subjects were classified into three groups according to their QFT and TST results in 2015 (QFT persistence positive, QFT-/TST + and QFT-/TST-). The serum levels of MCP-1 and IL-8 were significantly different among the three groups. Furthermore, level of IL-8 was dramatically lower in QFT-/TST- group as compared to the other two groups, and no significant difference was observed for QFT-/TST + group as comparing with persistent positive group. Our results suggested that the decreased serum level of IL-8 might be potential biomarker to identify QFT reversion caused by infection clearance.

ROLE OF APELIN/MONOCYTE CHEMOATTRACTANT PROTEIN-1, INFLAMMATORY, APOPTOTIC MARKERS IN THE REGULATION OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Objective: The objective of this study is to investigate blood nuclear factor κB (NF-κB), apelin, Lipid peroxide product ; thiobarbituric acid (TBA) malonaldehyde (MDA), monocyte chemoattractant protein-1 (MCP-1), B-cell lymphoma 2 (Bcl2), and paraoxonase (PON1) levels in patients with non -alcoholic fatty liver disease (NAFLD) in a trail to correlate the significance of these biomarkers in the diagnosis and initiation of NAFLD patients.Methods: A total of 32 patients with NAFLD and 45 healthy controls were enrolled in the study. Apelin levels were measured along with, NF-κB, MCP1, MDA, Bcl2, and PON1 were detected.Results: Significant increase in serum NF-κB, MDA, MCP1, and apelin levels in NAFLD patients with percentages increase 1031.23, 293.02, 165.93, and 120 %, respectively, while significant reduction in PON1 and BCl2 with percentages decrease 54.58 and 79.03 %, respectively, were detected as compared to controls. A significant correlation was found between serum concentration of the measured biomarkers with the incidence of NAFLD.Conclusions: It could be concluded that the patients with NAFLD have significantly increased circulating apelin, NF-κB, and MDA levels as compared to healthy control subjects while significant reduction in BCl2 and PON1 levels were recorded. Besides, the NAFLD status is tightly attributed to the existence of insulin resistance and oxidative stress.

Diallyl sulfide protects against lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in mice

The effects of diallyl sulfide (DAS) and the potential mechanisms were investigated on lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced acute liver injury in mice. DAS (50, 100, 200 μmol/kg) were orally given 1 h prior to LPS (10 μg/kg)/D-GalN (500 mg/kg) intraperitoneal injection. Serum and liver were collected at 8 h after LPS/D-GalN treatment. DAS Pretreatment reduced the activities of serum aminotransferase and attenuated histopathological damage in LPS/D-GalN-induced liver injury. Additionally, LPS/D-GalN-induced liver oxidative stress was ameliorated by DAS pretreatment, as evidenced by the decreased content of MDA and increased level of GSH, SOD, CAT in liver. Moreover, LPS/D-GalN-induced the excessive levels of TNF-α, IL-1β and MCP-1 in serum and liver was decreased by DAS pretreatment. Furthermore, DAS pretreatment attenuated LPS/D-GalN-induced hepatocyte apoptosis, as evidenced by TUNEL staining and protein expression of cleaved caspase3, Bax and Bcl-2 in liver. DAS also up-regulated the expression of p-PI3K p85 and p-Akt in a dose-dependent manner, and Akt inhibitor MK-2206 weakened the inhibitory effect of DAS on hepatocyte apoptosis induced by LPS/D-GalN. In conclusion, the results suggest that DAS exerts the protective effect on LPS/GalN-induced acute liver injury, and this effects possibly by suppressing oxidative stress, inflammation and regulating hepatocyte apoptosis via the PI3K/Akt pathway.

IL-17A+GM-CSF+ Neutrophils Are the Major Infiltrating Cells in Interstitial Lung Disease in an Autoimmune Arthritis Model.

To gain a better understanding of the pathogenesis of autoimmune arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD. We injected curdlan in SKG mice at 8 weeks of age, and identified the presence of ILD by PET-MRI at 20 weeks post-injection and histological analysis at 22 weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22 weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed. At 20 weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b+Gr1+ neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-α. Compared with 14 weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and soluble IL-7Rα had increased at 22 weeks post-injection, whereas those of IFN-γ, IL-22, IL-6, and TNF-α remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-α, were observed in immunofluorescent-stained lung tissue. We found that IL-17A+GM-CSF+ neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-α in ILD development.

Seroprevalence of Toxoplasmosis Antibodies among Diabetes Mellitus Patients and Assessment some Biochemical Markers

Toxoplasma gondii is an protozoan intracellular coccidian protozoan parasite. Latent toxoplasmosis threat to immunocompetent individuals. Diabetic patients are more susceptible to infect with toxoplasmosis due to their low level of immunity response. The purpose of this research is to define the association between toxoplasmosis and diabetes mellitus and detection serum levels of chemokines (monocyte chemoattractant protien-1 and transforming growth factor-β) in diabetic patients infected with toxoplasmosis. Serum samples were collected from 120 diabetic patients and 50 healthy individuals as a control group from the Imamein Kadhimein Medical City in Baghdad. In order to diagnose diabetes, fasting and random blood glucose tests were used . The diagnosis of toxoplasmosis was done by using toxo IgM and IgG immulite torch assay. Chemokines levels were measured by ELISA method. The results clarified that all samples were seronegative for IgM antibodies while 50 (41.67%) diabetic patients were seropositive for IgG antibodies and 70 (58.33%) diabetic patients and 50 healthy controls were seronegative for IgG antibodies. Serum level of MCP-1 was recorded an increase in a group of diabetic patients infected with toxoplasmosis 169.66 ± 131.35 pg/ml with highly significant differences (P &lt; 0.001) also TGF-β level was increased in a group of diabetic patients infected with toxoplasmosis 0.53 ± 0.242 pg/ml with highly significant differences (P ≤ 0.0001) when compare with the studied groups.

Moderate Exercise Suppresses NF-κB Signaling and Activates the SIRT1-AMPK-PGC1α Axis to Attenuate Muscle Loss in Diabetic db/db Mice.

The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db+Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance. Moderate exercise training prevented the loss of muscle mass of tibialis anterior and gastrocnemius muscles in db/db+Ex mice. The average cross-sectional area of tibialis anterior muscle was increased significantly in db/db+Ex mice compared with untrained mice (830.6 vs. 676.5 μm2). Inhibition of MuRF-1 and K48-linked polyubiquitination was observed in db/db+Ex mice. Exercise training reduced activation of IκBα/NF-κB pathway and lowered IL-6, TNFα, F4/80 (macrophage marker) at mRNA level in db/db+Ex mice compared with untrained mice. Exercise training did not influence FoxO3a phosphorylation and its upstream regulator Akt. Exercise training increased SIRT1 and PGC1α expression and AMPKα and mitochondrial complex IV activities and upregulated genes involved in mitochondrial biogenesis/function including Nrf1, Tfam, and mitochondrial complexes I–V. In conclusion, moderate exercise training inhibits NFκB signaling and activates SIRT1-AMPKα-PGC1α axis, thereby attenuating type 2 diabetes-related muscle atrophy.

Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus.

To assess T cell subsets and levels of chemokines and cytokines in patients with SLE and determine their relationships between disease activity and organ involvement. Blood samples from SLE patients (n = 24) and healthy controls (n = 36) were analyzed. Frequency of circulating follicular help T cells (Tfh), central memory T cells (Tcm), effector memory T cells (Tem), and naïve T cell subsets was enumerated and their surface markers expression of inducible T cell co-stimulator (ICOS) and programmed death 1(PD-1) protein was examined by flow cytometry. The disease state in SLE patients was evaluated using the SLE Disease Activity Index (SLEDAI). Concentrations of autoantibodies, serum C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), lgG, complement 3, complement 4, cytokines, and chemokines, such as IL-21, IL-17A, and IL-1β, were measured. The frequencies of circulating Tfh and Tcm cell subsets were significantly lower than those in healthy controls. However, the percentages of circulating PD1+ICOS+Tfh, PD1+ICOS+Tcm, and PD1+ICOS+Tem of PBMCs from SLE patients were higher than those in healthy controls. Furthermore, increased levels of serum IL-1β, IL-4, IL-6, MCP-1, IL-21, and IL-17A were detected in the patients with SLE compared to healthy controls. In addition, patients with immune thrombocytopenia displayed elevated proportions of serum IL-10, IL-17A, and IL-1β. Aberrant T cell subsets and cytokines expression profile were observed in SLE patients. PD1+ICOS+Tem cell subset was clearly influenced by disease activity and serum IL-10, IL-17A, and IL-1β were significantly increased in patients with immune thrombocytopenia. Therefore, PD1+ICOS+Tem cells might serve as an important tool for recognition and serum IL-10, IL-17A, and IL-1β might be an effective monitor for SLE patients with immune thrombocytopenia.

Interleukin-6 significantly improves predictive value of systemic inflammatory response syndrome for predicting severe acute pancreatitis

BackgroundPredicting severe acute pancreatitis (AP) is important for triage, prognosis, and designing therapeutic trials. Persistent systemic inflammatory response syndrome (SIRS) predicts severe AP but its diagnostic accuracy is suboptimal. Our objective was to study if cytokine levels could improve the predictive value of clinical variables for the development of severe AP. MethodsConsecutive patients with AP were included in a prospective cohort study at a tertiary care center. Serum levels of IL-6, TNF-α, IL-10, MCP-1, GM-CSF and IL-1β were measured at day 3 of onset of AP. Variables such as age, co-morbidity, etiology, SIRS, and cytokines were modeled to predict severe AP by multivariable regression analysis. Genotyping was done to correlate IL-6, TNF-α and MCP-1 gene polymorphisms with cytokine levels. ResultsOf 236 patients with AP, 115 patients admitted within 7 days of onset formed the study group. 37 of the 115 (32%) patients developed organ failure. Independent predictors of organ failure were persistent SIRS (OR 34; 95% CI: 7.2–159) and day 3 serum IL-6 of >160 pg/ml (OR 16.1; 95% CI:1.8–142). IL-6 gene (−174 G/C) GG genotype was associated with significantly higher levels of IL-6 compared to CC/CG genotype. Serum IL-6 >160 pg/ml increased the positive predictive value of persistent SIRS from 56% to 85% and specificity from 64% to 95% for predicting OF without compromising its sensitivity and negative predictive value. ConclusionSerum IL-6 of >160 ng/ml added significantly to the predictive value of SIRS for severe AP.

Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF

PurposeTo study the relationship between systemic pro-inflammatory factors and macular structural response to intravitreal bevacizumab for diabetic macular edema (DME). MethodsProspective study including 30 cases with DME, treated with bevacizumab and a minimum follow-up of 6 months. All cases underwent baseline laboratory testing for cardiovascular risk (high sensitivity C-reactive protein (hsCRP), homocystein), dyslipidemia, renal dysfunction and glucose control. Serum levels of VEGF, soluble ICAM-1, MCP-1 and TNF-α were assessed by enzyme-linked immunosorbent assay kits. Significant associations between systemic factors and quantitative and qualitative spectral-domain optical coherence macular features were analyzed. ResultsA mean of 4.82 ± 0.56 intravitreal injections was performed, resulting in significant improvement of central foveal thickness (CFT) (p < 0.001). A significant association with third month CFT decrease <10% was found for hsCRP (3.33 ± 2.01 vs 1.39 ± 1.15 mg/l, p = 0.007) and ICAM1 (975.54 ± 265.49 vs 727.07 ± 336.09 pg/ml, p = 0.012). ROC curve analysis indicated hsCRP and ICAM1 as significant biomarkers for 3rd month reduced anatomic response (area under the curve (AUC) = 0.807, p = 0.009 for hsCRP; AUC = 0.788, p = 0.014 for ICAM1). ROC curve analysis revealed hsCRP as a significant biomarker for 6th month CFT decrease <10% (AUC = 0.903, p < 0.001, cutoff value = 1.81 mg/l). A significant association with 6th month CFT decrease ≥25% was found for serum MCP1 (244.69 ± 49.34 pg/ml vs 319.24 ± 94.88 pg/ml, p = 0.017) and serum VEGF (90.84 ± 37.33 vs 58.28 ± 25.19 pg/ml, p = 0.027). The combined model of serum VEGF and LDL-cholesterol was found to be predictive of 6th month hard exudate severity (p = 0.001, r2 = 0.463). ConclusionsIncreased levels of hsCRP and ICAM1 were found to be significant biomarkers for early reduced anatomic response to anti-VEGF treatment. Cases with higher serum levels of such factors had increased CFT values, despite treatment, suggesting inner blood-retinal barrier breakdown that is not adequately responsive to anti-VEGF monotherapy.