Expression level and clinical significance of SOCS1 in the serum of patients with chronic HBV-related liver disease / 西安交通大学学报(医学版)

【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.

A novel inhibitor of N 6-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities

N 6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Research progress on the role of miR-155 in rejection of organ transplantation / 器官移植

Rejection has constantly been an unresolved challenge in the field of organ transplantation. The research on the mechanism of rejection plays a significant role in improving the efficacy of organ transplantation and enhancing the survival rate of graft. The innate and specific immune responses of the human body jointly participate in the graft rejection, leading to graft injury. In recent years, multiple researchers have conducted in-depth studies on the mechanism underlying the role of microRNA (miR) in regulating rejection. Among them, miR-155 has been widely considered as a key factor involved in immune regulation. The expression level and functional status of miR-155 may be intimately associated with the occurrence of rejection, which may become a new target for overcoming rejection. In this article, relevant studies on the role of miR-155 in regulating key immune cells in innate and specific immune responses were reviewed, aiming to provide novel ideas for the development of new immunosuppressants and rejection therapy.

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (

Effect of Low Expression of Vitamin D Receptor on Immune Response in Patients With Primary Biliary Cholangitis / 胃肠病学

Background: Immune function plays a key role in the development of primary biliary cholangitis (PBC). Vitamin D plays an immunomodulatory role through vitamin D receptor (VDR) and may participate in the development and progression of PBC. Aims: To investigate the effect of low expression of VDR on immune response in patients with PBC. Methods: Thirty patients with PBC were enrolled, and 30 patients with non-PBC were served as controls. mRNA expressions of VDR, SOCS-1, miR-155 in liver tissue and peripheral blood mononuclear cell (PBMC) were detected by real-time quantitative PCR, protein expressions of VDR, SOCS-1 were measured by Western blotting and immunohistochemistry. Expressions of VDR, SOCS-1 and miR-155 in liver tissue and PBMC were compared between PBC group and control group. Correlations of expressions of VDR, SOCS-1 and miR-155 in liver tissue in patients with PBC were analyzed. Results: Compared with control group, mRNA and protein expressions of VDR and SOCS-1 were significantly decreased (P<0.05), and expression of miR-155 in liver tissue was significantly increased in PBC patients (P<0.05). The mRNA and protein expressions of VDR and SOCS-1 in PBMC were significantly decreased in PBC group than in control group (P<0.05). There was a significant positive correlation between VDR protein and SOCS-1 expression and a negative correlation between expressions of miR-155 and VDR, SOCS-1 in liver tissue of PBC patients. Conclusions: The expression of VDR in patients with PBC is significantly decreased. VDR may be involved in the regulation of development and progression of PBC through miR-155 and SOCS-1.

Study on influence of the CpG DNA on activation of IFN-γ signaling transduction regulatory proteins / Монголын Анагаах Ухаан

Introduction@#When human body encounters external pathogens primary/innate immunity cells are activated by recognizing them and secondary/adaptive immunity is activated consecutively. In our previous study, we revealed that there is a synergistic action between TLR9 and IFN-γ signaling in the endothelial cells. @*Purpose@#To determine the role of negative and positive regulator proteins on the IFN-γ/TLR9 signaling pathway. @*Methods@#In this study, murine endothelial cell (END-D) culture was used. END-D cells pre-treated with TLR9 ligand CpG DNA and then stimulated with IFN-γ. The negative (SHP-2, SOCS1, PIAS1) and positive (p38) regulator protein expression was detected by Western blotting. @*Results and Conclusion@#Treatment by TLR9 ligand CpG DNA and IFN-γ increased positive regulator p38 phosphorylation in 0.5 hour. CpG DNA inhibited IFN-γ negative regulator PIAS1 protein expression in 6 hour and SOCS1 and SHP-2 expression could not affect in 4 hour.

Effects of Different Stimulation of Electroacupuncture on Protein Expressions of SOCS1 and SOCS3 in Rabbits with Acute Facial Nerve Injury / 中国中医药信息杂志

Objective To investigate the effects of different stimulation of electroacupuncture on the protein expressions of SOCS1 and SOCS3 in rabbits with acute facial nerve injury; To determine the better stimulation. Methods New Zealand rabbits were treated with special hemostatic forceps for 5 min, and the length of the lesion was about 2.5 cm. The model of facial nerve injury was induced. The experiment was divided into blank group, sham-operation group, model group, and electoracupuncture weak-, medium-, and strong-stimulation group. The model group received no intervention after surgery. After treatment, the damaged facial nerve of each group was intercepted. The protein expressions of SOCS1 and SOCS3 mediated by negative feedback regulation of JAK-STAT were detected by ABC-ELISA. Results Compared with the blank group, the protein expressions of SOCS1 and SOCS3 in the model group increased (P<0.01). Compared with the model group, the protein expressions of SOCS1 and SOCS3 protein in electroacupuncture weak- stimulation group decreased (P<0.01). Conclusion Electroacupuncture can make SOCS1, SOCS3 protein expressions normal for acute facial nerve injury, and acupuncture treatment effect does not increase with the increase of stimulation.

Detection and the Significance of SOCS-1 Gene Methylation Status in Peripheral Blood of Systemic Lupus Erythematosus Patients / 现代检验医学杂志

Objective To investigate the relationship between the systemic lupus erythematosus (SLE)and the SOCS-1 gene methylation status of the peripheral blood DNA,to provide the basis for diagnosis and treatment of systemic lupus erythema-tosus.Methods Blood samples of SLE patients (27 cases)and healthy group (19 cases)in January 2015 to April were col-lected and the DNA were extracted.Using polymerase chain reaction combining DNA agarose gel electrophoresis to detect the SOCS-1 gene methylation status.Results In patients with systemic lupus erythematosus SOCS-1 gene complete methyl-ation accounted for 44% (12/27),incomplete methylation accounted for 56% (15/27).In healthy group SOCS-1 gene com-plete methylation accounted for 74% (14/19)and incomplete methylation accounted for 26% (5/19).The rate of complete methylation of SOCS-1 gene of SLE patients was lower than that of healthy group (χ2=3.88,P=0.049).Conclusion SLE patients may have lower SOCS-1 gene methylation status in the peripheral blood DNA,which is worth for further study.

Protective Effects and Underlying Mechanisms of Compound Herba Houttuyniae in db/db Mice / 中草药·英文版

Objective Houttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine (TCM) compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical therapy for diabetic nephropathy. On the basis of the TCM theory of heat in diabetes mellitus and the clinical efficacy of Fructus Arctii, the two compounds were used to develop a formula named Compound Herba Houttuyniae. This study evaluated the renoprotective effects of different Compound Herba Houttuyniae extracts and assessed their mechanisms through the Janus kinase/signal transducer and activator of transcription (JAK/STAT)-suppressors of cytokine signaling (SOCS)-1 pathway. Methods The normal group comprised db/m mice (n = 8); db/db mice were randomly divided into six groups according to the applied treatment method: model group (no treatment), AG490 group, petroleum ether extract (PEE) group, ethyl acetate extract (EAE) group, N-butanol extract (NE) group, and water extract (WE) group (n = 6 in each group). The general status, biochemical indicators, and renal histological changes in the mice were evaluated, and the JAK/STAT-SOCS-1 pathway was assessed. Results The NE and WE groups showed a decrease in 24-h urinary protein and albumin levels as well as serum uric acid and fibronectin levels but showed no changes in fasting plasma glucose and hemoglobin A1c levels. The protein expression of JAK2, STAT3, P-JAK2, and P-STAT3 and the gene expression of JAK2 and STAT3 in kidney tissues were significantly increased (P < 0.05) in the model group. Compared with the model group, the expression of P-JAK2 and P-STAT3 was downregulated in the extract treatment groups. The expression of SOCS-1 was increased in the NE and WE groups (P < 0.05). However, the expression of JAK2, STAT3, JAK2mRNA, and STAT3mRNA in the treatment groups did not show any significant differences. Conclusion Compound Herba Houttuyniae showed renoprotective effects in db/db mice, and the strongest effects were observed in the WE and NE groups. The underlying mechanism for these effects might involve the regulation of the JAK/STAT-SOCS-1 pathway.

Effects of DNMT1-siRNA on the pain behavior and the expression of SOCS1,p-ERK,p-CERB in CCI rats / 临床麻醉学杂志

Objective To investigate the effects of DNMT1 on neuropathic pain behavior and neuropathic pain modulation.Methods Thirty-two male SD rats, weighing 200-250 g, were randomly assigned into 4 groups (n =8 each):sham operation group (group S),chronic constrictive injury group (group CCI),CCI+ DNMT1-siRNA group (group CDS),CCI+ control-siRNA group (group CCS).Group CDS were intrathcally injected of DNMT1-siRNA (2 μg/10 μl),and group CCS were intrathcally injected of control-siRNA 7,8,9 days after operation.Mechanical withdrawal threshold (MWT)and thermal withdrawal latency (TWL)were measured before operation and on day 3,5,7,9,12,14 after operation.The rats were then sacrificed and L4-L6 segments of the spinal cord were removed for determination of SOCS1,p-ERK,p-CREB expression using Western blot on day 14.Results Compared with group S,MWT and TWL in group CCI and CCS were significantly decreased on day 3,5,7,9,12,14 after operation (P <0.05).Compared with group CCS,MWT and TWL in group CDS were significantly increased on day 9,12,14 after operation (P < 0.05 ). Compared with group S and CDS,SOCS1 was significantly downregulated,p-ERK and p-CREB were significantly upregulated in group CCI and CCS (P <0.05 ).Conclusion Intrathcal injection of DN-MT1-siRNA significantly relieves neuropathic pain by upregulating SOCS1,downregulating p-ERK and p-CREB in rats spinal cords.

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.

Effects of aggressive dosing of atorvastatin on the expression of SOCS1 in CD4 + Tlymphocytes from patients with unstable angina pectoris during peri-operative period of PCI / 中华急诊医学杂志

Objective To investigate the effects of aggressive dosing of atorvastatin on the expression of SOCS1 in CD4 + Tlymphocytes from patients with unstable angina pectoris during peri-operative period of PCI.Methods A cohort of 50 patients with unstable angina pectoris were randomized (random number) to give pretreatment with either an aggressive dose (80 mg/d,n =25) or a routine dose (20 mg/d,n =25)of atorvastatin.Circulating CD4 +T cells were subsequently obtained prior to PCI,and also 18 h to 24 hours after PCI,using a magnetic cell sorting system (MACS).Fluorescence-based quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure expressions of SOCSI mRNA in the isolated CD4 + Tlymphocytes,and western blot analysis was used to detect levels of SOCS1 protein.Serum levels of IFN-γwere quantified using enzyme-linked immunosorbent assays (ELISAs).Results Compared with routine dose group,the expressions of SOCS1 mRNA and protein levels were dramatically increased and those were higher in aggressive dose group following PCI (P ＜ 0.05).In contrast,serum levels of IFN-γsignificantly increased following PCI in both groups,but it was higher in routine dose group than in aggressive dose group (P ＜ 0.05).Conclusions Treatment with aggressive dosing of atorvastatin reduced the post-PCI myocardial inflammatory response in patients with unstable angina pectoris,possibly modulating by up-regulating SOCS1 expression in CD4 + Tlymphocytes.

Carboxymethytl pachymaram induces the methylation of SOCS-1 gene and the maturation of human monocyte-derived dendritic cells / 中华微生物学和免疫学杂志

Objective To investigate the effects of carboxymethytl pachymaram ( CMP ) on the methylation of SOCS-1 (suppressor of cytokine signaling-1) gene and the in vitro maturation of human mono-cyte-derived dendritic cells (DCs).Methods Human DCs were induced from the peripheral blood mono-cytes in vitro with the treatment of recombined human GM-CSF and interleukin-4 ( IL-4 ) and cultured with different concentrations of CMP (10, 50, and 100 mg/L).The methylation and expression of SOCS-1 gene were analyzed by methylation-specific polymerase chain reaction (MSP) and real-time PCR, respectively. The phenotypic markers of DCs were detected by flow cytometry .Mixed lymphocyte reaction ( MLR) and ELISA were performed to measure the lymphocyte proliferation induced by DCs and IL-12 secretion by DCs . Results CMP promoted the methylation of SOCS-1 gene, but inhibited the expression of SOCS-1 gene in dendritic cells at the concentrations of 50 mg/L and 100 mg/L.The expression of phenotypic markers (CD80, CD83, CD86 and HLA-DR), IL-12 secretion and lymphocyte proliferation induced by DCs were significantly enhanced in a dose dependent manner with the treatment of CMP .Compared with control group , the levels of methylated SOCS-1 gene and IL-12 and the lymphocyte proliferation index were increased upon the stimulation with 50 mg/L and 100 mg/L of CMP (P<0.01), but the expression of SOCS-1 gene was de-creased.The expression of CD80, CD83 and HLA-DR on DCs in the presence of 100 mg/L of CMP were higher than those of control group (P<0.05).Conclusion CMP could induce the methylation of SOCS-1 gene and the maturation of DCs derived from peripheral blood monocytes .

Suppression of miR-155 Expression in IFN-gamma-Treated Astrocytes and Microglia by DJ-1: A Possible Mechanism for Maintaining SOCS1 Expression

Previously, we reported that DJ-1, encoded by a Parkinson's disease (PD)-associated gene, inhibits expression of proinflammatory mediators in interferon-gamma (IFN-gamma)-treated astrocytes and microglia through inhibition of STAT1 activation. Here, using microglia and astrocytes cultured from wild-type (WT) and DJ-1-knockout (KO) mouse brains, we examined how DJ-1 regulates suppressor of cytokine signaling 1 (SOCS1), a negative feedback regulator of STAT1 (signal transducer and activator of transcription) that is also induced by STAT1. We found that IFN-gamma significantly increased SOCS1 mRNA expression in WT microglia and astrocytes, but not in KO cells, although STAT1 was highly activated in these latter cells. We further found that SOCS mRNA stability was decreased in DJ-1-KO cells, an effect that appeared to be mediated by the microRNA, miR-155. IFN-gamma increased the levels of miR-155 in DJ-1-KO cells but not in WT cells. In addition, an miR-155 inhibitor rescued SOCS1 expression and decreased STAT1 activation in DJ-1-KO cells. Taken together, these results suggest that DJ-1 efficiently regulates inflammation by maintaining SOCS1 expression through regulation of miR-155 levels, even under conditions in which STAT1 activation is decreased.

Study on aberrant methylations of SHP-1, p15 and SOCS-1 genes in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To detect the significance of the SHP-1,p15 and SOCS-1 genes methylation status in the genesis and development of diffuse large B-cell lymphoma (DLBCL).Methods The methylation state of SHP-1,p15 and SOCS-1 genes CpG islands were measured by methylation-specific polymerase chain (MSP) reaction.Results The positive rates of aberrant methylation for SHP-1,p15 and SOCS-1 genes in 50 specimens of DLBCL were 96 ％ (48/50),52 ％ (26/50) and 56 ％ (28/50) respectively.In control group,however,15 specimens of benign lymph node proliferation showed no methylation in CpG island of SHP-1,p15 and SOCS-1 genes promoter.Conclusion Aberrant methylations of the SHP-1,p15 and SOCS-1 genes exist in the patients with DLBCL.The methylations of SHP-1,p15 and SOCS-1 genes may be associated with the occurrence and development of DLBCL.This study provides a theoretical basis of treatment methylation for DLBCL.

Effects of arsenic trioxide on intracelluar SOCS-1 gene methylation and P-STAT3 expression in multiple myeloma cells / 国际肿瘤学杂志

Objective To investigate the effects of arsenic trioxide (AS2O3)on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells.Methods MM cell lines U266 and CZ-1 were used as in vitro models.Methylation status of SOCS-1 gene was detected by the methylation specific PCR (MSP)while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment.Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry.Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type.After exposure to AS2O3,it was shown that SOCS-1 gene was demethylated obviously,meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line.The apoptosis rate was increased.When U266 and CZ-1 were treated with AS2O3 of 0,0.5,1.0,2.0 μmol/L respectively,the total cell apoptosisis ratio of U266 was 0.06％,0.56％,48.96％,61.07％ (X2 =9.19,P ＜ 0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2％,,40.3％,,47.72％,,68.49％ (X2 =8.96,P ＜0.05 ).Conclusion AS2O3 could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.

The role of activation of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease / 中华微生物学和免疫学杂志

Objective To investigate the role of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease(KD). Methods Forty-eight children with KD and eighteen age-matched healthy children were consented to participate in this study. Protein concentration of IL-6 in plasma was measured by ELISA. Transcriptional levels of IL-17A, IL-17F, RORγt, Foxp3, SOCS1 and SOCS3 were assessed by real-time PCR. The proportion of CD4+CD25+Foxp3+ regulatory T(Tr) cells and mean fluorescence intensity(MFI) for phosphorylated-STAT3(pSTAT3) protein in CD4+ T cells was analyzed by flow cytometry. A quantitative methylation specific PCR based on SYBR Green was used to evaluate methylation status of CpG islands in SOCS1 exon2, three potential bind sites for STAT3 in 5'-untraslated region(5'-UTR) of SOCS3 in CD4+ T cells. Results (1)Compared with healthy volunteers, plasma IL-6 concentration and MFI for pSTAT3 in CD4+ T cells were elevated significantly during acute phase of KD[IL-6:(54.02±20.58) pg/ml vs (8.72±2.06) pg/ml, P0.05). ConclusionAberrant activation of IL-6/STAT3 signaling caused by hypomethylation of SOCS1 and SOCS3 might be one contributing factor to unbalance of Th17/Tr in KD.

Study on the Expression of Suppressor of Cytokine Signaling -1 ( SOCS1 ) in the Liver of Septic Mice / 中华急诊医学杂志

Objective To investigate the change of the content of suppressor of cytokine signaling (SOCS-1) in the liver of septic mice and its working mechanism.Methods Adopted Cecalligation and puncture (CLP) to create models of sepsis and divided randomly adult male BALB/c mice into 8 groups,including normal controlled group,sham-operated group,and the killed groups 2 hours,6 hours,12 hours,24 hours and 48 hours after operation.After extracting the RNA and protein from the liver tissue of the mouse groups,reverse transcription polymerase chain reaction (RT-PCR) was adopted to determine the relative content of SOCS-1 mRNA in the tissue,Western blot was adopted to determine the relative content of protein and the SPSS statistics software was adopted to calculate the correlation.Then observed the pathological change of liver tissues,and detected SOCS-1 protein expression by immunohistochemistry.Results After CLP suergery,the expression of SOCS-1 on gene degree in the liver and the expression of SOCS1 on protein degree in the liver increased rapidly at the 6th hour ( P ＜ 0.05 ),with the former reaching peak ( P ＜ 0.05 ) at the 24th hour and the latter remaining high all the time.There were pathological changes such as fatty degeneration and necrosis in the septic liver tissue,hepatic SOCS-1 protein expression could be detected by immunohistochemistry.Conclusions CLP induced sepsis could lead to the increase of the expression of SOCS1 in the liver.

Function of suppressors of cytokine signaling 1 in dendritic cells-based tumor vaccines / 国际肿瘤学杂志

Dendritic cells (DCs) are the important auxiliary cells in tumor vaccines to activate antitumor immunity.Suppressor of cytokine signaling 1 ( SOCS1 ) has been shown to play an important role in inhibition of cytokine signal transduction.Recent studies show that inhibition of the function of SOCS1 in DCs plays a critical role in strongly enhancing tumor vaccines antitumor activity,and in the methods of restraining SOCS1 's function have also made significant progress.

Influence of SOCS1 and SOCS3 hypomethylation on homeostasis of Th1/Th2 in Kawasaki disease / 中华风湿病学杂志

Objective To investigate the effect of SOCS1 and SOCS3 hypomethylation on homeostasis of Th1/Th2 in Kawasaki disease(KD). Methods Thirty-six children with KD and sixteen age-matched healthy children consented to participate in this study. Protein concentration of IL-6 in plasma was measured by ELISA. Transcriptional levels of SOCS1, SOCS3, T-bet, IFN-γ, GATA3 and IL-4 were assessed by realtime PCR. The proportion of Th1 and Th2 cells, and mean fluorescence intensity(MFI)for phosphorylated STAT3(pSTAT3)protein in CD4+ T cells was analyzed by flow cytometry. A quantitative methylation specific PCR based on SYBR Green was used to evaluate methylation status of CpG islands in SOCSl exon2, and three potential binding sites for STAT3 in 5'-untraslated region(5'-UTR)of SOCS3 in CD4+T cells. Comparisons between groups were performed with t-test. Results ①Compared with healthy volunteers, plasma IL-6 concentration[(51.8±16.3)pg/ml vs(8.6±2.0)pg/ml, respectively]and MFI for pSTAT3[(52±14)vs(10±4), respectively]in CD4+ T cells were elevated significantly during acute phase of KD(P＜0.05), and the two items in KD patients with coronary artery lesion(KD-CAL+)were found to be higher than those in KD patients without coronary artery lesion(KD-CAL-)[IL-6:(87.2±27.4)pg/ml vs(36.2±12.8)pg/ml, P＜0.05; pSTAT3 MFI:(75±15)vs(42±11), P＜0.05]. ② The proportions of Th1 and Th2 cells and transcription levels of Th-associating factors(T-bet, IFN-γ, GATA3 and IL-4)in CD4+ T cells increased significantly in acute KD(P＜0.05), while the rate of Thl div Th2 in KD patients was found to be lower than that in normal controls(P＜0.05). In addition, the proportions of Th1 and Th2 cells and expressions levels of Th-associating factors in KD-CAL+ group were higher than those in KD-CAL-group, as well as the rate of Thl div Th2 cells in KD -CAL+ group were lower than that in KD-CAL- group(P＜0.05). ③ The mRNA levels of SOCSl and SOCS3 in CD4+ T cells increased significantly during acute phase of KD(P＜0.05), while the two items in KDCAL+ group were lower than those in KD-CAL- group(P＜0.05). Furthermore, CpG islands in SOCSl exon2 and the third potential binding site for STAT3 in SOCS3 5'-UTR were hypomethylated in acute KD, while those in healthy volunteers were fully demethylated(P＜0.05). Demethylation levels of the two items mentioned above in the KD-CAL+ group were lower than those in the KD-CAL-group(P＜0.05). CpG islands in the other two binding sites for STAT3 in SOCS3 5'-UTR were fully demethylated among all the groups(P＞0.05).Conclusion Relative insufficiency of SOCS1 and SOCS3 expression caused by hypomethylation may be one contributing factor for the imbalance of Th1/Th2 in KD.