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Objective:To investigate the clinical features and influencing factors of renal artery involvement in patients with Takayasu's arteritis (TA).Methods:One hundred and five TA patients were included and their clinical features, laboratory tests, echocardiographic findings were collected and analyzed. The t-test, Mann-Whitney U test, Sperman's correlation and logistic regression were used for statistical analysis. Results:Of the 105 patients with Takayasu's arteritis, 21 (20%) patients were diagnosed to have renal artery involvement. They had higher frequency of hypertension [76%(16/21) vs 25%(21/84); χ2=19.291, P<0.01], syncope [19%(4/21) vs 4%(3/84); P=0.028] and headache [52%(11/21) vs 25%(21/84); χ2=5.944, P=0.019]. Patients with renal artery invol-vement had higher levels of creatinine [(67±30) mmol/L vs (50±14) mmol/L; t=2.436, P=0.023], lower levels of lymphocyte subsets CD3 +[1 299(1 261.5, 1 313.45)/μl vs 1 531 (1 330, 1 559.5)/μl; Z=-3.12, P=0.002], CD4 +[793.6(715, 804.32)/μl vs 914.88(794.3, 914.8)/μl; Z=-2.597, P=0.009], CD8 +[451.09(451.09, 489.5)/μl vs 552.39(459.75, 557.5)/μl; Z=-3.271, P=0.001] and glomerular filtration rate ( Z=-2.612, P=0.009). Comparison of echocardiographic parameters between the two groups showed that the diameters of left atrium [(35±4) mm vs (32±4) mm; t=3.065, P=0.003] and end-diastolic left ventricular [49.2(47.5, 52.5) vs 45.84(43.25, 47.75); Z=-3.795, P<0.01] were larger in renal artery involvement group. Abdominal aorta ( χ2=14.292, P<0.01), superior mesenteric artery ( P<0.01), inferior mesenteric artery ( P=0.038) and common iliac artery ( P=0.005), were more likely involved in patients with renal artery involvement; while the common carotid artery ( χ2=3.815, P=0.047) and subclavian artery ( P=0.022) were less affected. There was a positive correlation between creati-nine level ( r=0.282, P=0.004) and renal artery involvement in patients with arteritis, and the number of lymphocyte subsets (CD3, CD4, CD8) ( r=-0.306, P=0.002; r=-0.255, P=0.009; r=-0.321, P=0.001) was negatively correlated with renal artery involvement. Conclusion:The most common pattern of renal artery involvement is stenosis and occlusion. Hypertension, syncope, headache, kidney dysfunction and heart failure are more prevalent among patients with renal artery involvement. The number of lymphocyte subsets is low, and involvement of abdominal aorta is common. It should be assessed and treated as soon as it is discovered.
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Objective To study the mental status and its influencing factors of patients with rheumatic disease. Methods Three hundreds and eighty-one patients with rheumatic diseases were assessed with the self-rating anxiety scale, self-rating depressive scale, Eysenck Personality Questionnaire symptom checklist-90, and demographic characteristics questionnaire. The comparison among groups were tested by t tests, Spearman's correlation analysis. Results Patients with anxiety symptoms accounted for 35.96%, and pre-valence rate of depression was 48.03%. The gender (r=0.87, OR=2.34) and duration (r=0.006, OR=1.006) were the risk factors and the C4 (r=-2.63, OR=0.07) was the protective factor. In patients with systemic lupus erythematosus, depression was related to education (Z=2.228, P=0.026), disease duration (Z=-2.015,P=0.044), IgG level (t=-2.266, P=0.027), T cell subsets CD8 (Z=1.981, P=0.047) and CD3 (Z=1.967, P=0.049). Anxiety was related to education (Z=2.452, P=0.014), duration (Z=-2.054, P=0.04), complement C3 (t=2.035, P=0.045), C4 (Z=-2.204, P=0.028) and IgG level (t=-2.126, P=0.036). The value of CRP(Z=-1.984, P=0.047) and IgM (t=2.243, P=0.028) of rheumatoid arthritis patients were higher in the depression group. The depression group was different in disease duration (Z=-2.631, P=0.009), gender ( χ2=4.415, P=0.042), ESR (Z=2.17, P=0.023) and CD3 cell (Z=2.023, P=0.043) in Sj?gren's syndrome patients. Correlation analysis showed positive correlation between the score of SDS, SAS and the P value (r=0.21, P=0.01) (r=0.14, P=0.007) N dimension (r=0.52, P=0.01) (r=0.55, P=0.007) of EPQ. There were negative correlation between the score of SDS, SAS and the E dimension (r=-0.23, P=0.01) (r=-0.14, P=0.006) of EPQ. Conclusion The prevalence of depres-sion and anxiety is higher in patients with depressive and anxious symptoms. They are in older age, female gender, poor education, longer duration, lower complement and lower T cell subsets when compared with those patients without depression and anxiety. Patients who have an introverted, instable, nervous temperament are more likely to be depressed and anxious. Psychological assessment intervention and therapy should be carried out as early as possible.
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Objective To silence the expression of CTGF by small interfering RNA technology,to observe the influence on fibroblast?like synovial cell apoptosis and several apoptosis?related genes,and to explore the mechanism of action of CTGF in rheumatoid arthritis synovial lesions. Methods Effective CTGF siRNA was screened through real?time PCR. The influence of CTGF siRNA on FLS apoptosis was detected with FITC?PI double staining by flow cytometry. bax,bcl?xl and survivin were detected using real?time PCR when CTGF mRNA has been silenced. Results Compared with other 2 groups of oligo and NC oligo,H1 oligo exhibited the strongest interfering action to CTGF(inhibition ratio>70%),so that it is selected as the effective target gene sequence for the following experiment. Apoptosis of FLS induced by serum deprivation was significantly decreased in the presence of exogenous CTGF. When expression of the CTGFgene was knocked down in FLS,FLS apoptosis was significantly increased,and expres?sion levels of survivin mRNA were decreased significantly(P<0.01). Conclusion FLS survival is positively regulated by CTGF,which may through the sustaining the expression of survivin.
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Objective To investigate the expression levels of Interleukin(IL)?6 and matrix metalloproteinases(MMP)?13 in synovial fluid by in?vigorating kidney and activating blood formulae in treating rabbit knee osteoarthritis model. Methods A total of 30 New Zealand rabbit were ran?domly divided into blank group,model group,invigorating kidney group,activating blood group and invigorating kidney and activating blood group. Rabbits model with knee osteoarthritis were established by improved Hulth method. To give corresponding respectively the medicinal broth,model group was given saline,knee joint synovial fluid was collected after 4,8 and 12 weeks. Enzyme linked immunosorbent assay(ELISA)was used to measure the levels of IL?6 and MMP?13. Results The levels of IL?6 in rabbit knee osteoarthritis were obviously higher than that of normal control group at both 4 weeks and 8 weeks(P<0.001). But there was no statistical difference on the levels of IL?6 compared with controls in 12 weeks. In addition,the level of MMP?13 at 4 weeks,8 weeks and 12 weeks were significantly higher than the blank control group(P<0.001). After 8 weeks of Chinese medicine administration,the levels of IL?6 in synovial fluid were significantly decreased in invigorating kidney group,activating blood group and invigorating kidney and activating blood group(P<0.001),but there was no statistical difference among groups in 12 weeks. The MMP?13 levels of synovial fluid was significantly lower than the model group(P<0.001). Conclusion Our results indicate that IL?6 and MMP?13 par?ticipate in the pathological development of the rabbit knee osteoarthritis. Invigorating kidney and activating blood formulae could reduce the expres?sion of IL?6 and MMP?13 and alleviate osteoarthritis progression,and which is superior to the pure invigorating kidney formulae and activating blood formulae.
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Objective To investigate the effect of galectin-3 (Gal-3) on the pathogenesis of primary biliary cirrhosis (PBC).Methods The clinic data of 72 PBC patients at different stages were analyzed and the serum levels of Gal-3 were detected in 72 PBC patients and 20 controls by enzyme linked immunosorbent assay (ELISA).Independent t-test,variance analysis,LSD-t and Pearson correlation analysis were adopted for data analysis.Results The serum Gal-3 levels were significantly higher in PBC patients than those of healthy controls [(855±634) pg/ml,(463±446) pg/ml,P<0.05].With the progression of disease,the levels of Gal-3,platelets,hemoglobin,albumin,IgM and complement C3 gradually declined,but the level of total bilirubin gradually elevated(P<0.05).There was positive correlation between Gal-3 and immunoglobin IgM,complement C3 levels (r=0.330,P=0.005; r=0.357,P=0.002).There was negative correlation between Gal-3 and total bilirubin levels (r=0.350,P=0.003).Conclusion The Gal-3 can participate in the immune-mediated inflammation of PBC and the formation of liver fibrosis.The levels of Gal-3,platelet count,hemoglobin,albumin,IgM,complement C3 and total bilirubin could be regarded as laboratory parameters for the evaluation of the disease severity and prognosis.
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Objective To investigate the profiles of serum nerve grow factor profile (NGF),neurotrophin (NT)-3,as well as brain-derived neurotrophic factor (BDNF) in patients with dermatomyositis (DM) complicated with interstitial lung damage (ILD).Methods Forty-seven patients were divided into 2 groups:ILD group (30 patients) and non-ILD group (17 patients).Twenty healthy blood donors were used as controls.Serum levels of NGF,NT-3,as well as BDNF were measured serum by enzyme-linked immunosorbent assay (ELISA).ANOVA was used to compare serum level of NTs.When a significant difference was found,the exact P-values were calculated using the student's t-test or t-test followed by Bonferroni's correction.Pearson test was used for correlation analysis.Results The serum NGF levels in healthy control group,the non-ILD group and the ILD group were (182±43),(308±72),(480±96) pg/ml respectively.There was statistically significant difference between the three groups (F=90.3,P<0.01),and the serum NGF levels were elevated significantly in ILD and non-ILD patient groups as compared with healthy controls (t=12.9 and t=6.5 respectively,both P<0.01).The serum level of NGF was significantly higher in ILD group than that in the non-ILD group (t=6.4,P<0.01).There was no significant difference in the serum levels of NT-3 among the two patient groups and healthy controls.On the contrary,BDNF levels were significantly decreased in both ILD [(792± 106) pg/ml] and non-ILD patients groups [(963±93) pg/ml] when compared with healthy controls [(1 281±107) pg/ml] (t=15.9 and t=9.6 respectively,both P<0.01).The decrease was also significant in ILD group when compared with non-ILD group (t=5.6,P<0.01).Moreover,NGF and BDNF both showed significant correlation with serum C-reactive protein (CRP) level in ILD group by applying Pearson correlation analysis (r=0.56,P<0.01; r=-0.48,P<0.05 respectively).Conclusion Neurotrophins may play an import role in the pathogenesis of DM.
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Objective To investigate the clinical features and outcome of retroperitoneal fibrosis (RPF).Methods Thirty-three cases of RPF treated in the Department of Rheumatology and Immunology were analyzed retrospectively,including the clinical characteristics and laboratory data.Results RPF occurred predominantly in elderly men with untypical clinical manifestations such as back pain,abdominal pain and lower limb edema.In laboratory tests,the inflammatory parameters such as erythrocyte sedimentation rate and C-reactive protein increased significantly,and renal function failure was frequent finding in patients with urethral obstruction.All patients had retroperitoneal soft tissue image or urethral obstruction on computed tomography or magnetic resonance imaging,four of which had histological diagnosis of idiopathic RPF.Twenty-three patients received surgical interventions.Eighteen patients received medical treatment alone including corticosteroids,immunosuppressants,and tamoxifen.Nine patients received corticosteroids after surgical intervention.Surgery and medical treatments are effective for idiopathic RPF.Conclusion Image examination is valuable in diagnosis and differential diagnosis of PRF.Pathological diagnosis is the golden standard.Long-term low dose corticosteroids and immunosuppressants may prevent relapse of idiopathic RPF.
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OBJECTIVE: Our previous studies indicated that CD40-mediated Fas-dependent apoptosis is important for the glandular destruction of Sjögren's syndrome (SS), although other immune and nonimmune mechanisms are also involved in exocrine dysfunction. We investigated the roles of p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-κB (NF-κB) in salivary epithelial cell death in SS. METHODS: Expression of p38, phosphorylated p38 (pp38), and IκB-α was examined by Western blotting upon CD40 ligation. Activity of NF-κB induced by anti-CD40 monoclonal antibody (mAb) was examined by electrophoretic mobility shift assay (EMSA) and Western blotting. Expression of Fas was analyzed by flow cytometry and Western blotting with or without the p38-specific inhibitor SB203580 or the NF-κB-specific inhibitor caffeic acid phenethyl ester (CAPE). Induction of apoptosis in salivary epithelial cells was examined by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Expression of phosphorylated p38MAPK and NF-κB was measured by immunohistochemistry. RESULTS: pp38MAPK and NF-κB p65 were predominantly expressed in the ductal and acinar epithelium adjacent to lymphoid infiltrates of SS salivary gland by immunohistochemistry. CD40 ligation strongly enhanced p38MAPK and NF-κB activity by EMSA and Western blotting in cultured salivary epithelial cells. Treatment of cells with anti-CD40 mAb resulted in significantly upregulated Fas expression and induction of Fas-dependent apoptosis. Inhibition of p38MAPK and NF-κB activity by SB203580 and/or CAPE reduced Fas expression and apoptosis in salivary epithelial cells, establishing p38MAPK and NF-κB as proapoptotic factors in this context. CONCLUSION: CD40 ligation plays an important role in activation of p38MAPK, NF-κB, and Fas molecules to initiate proapoptotic signaling. p38MAPK and NF-κB collaborate in regulation of proapoptotic signaling in CD40-mediated Fas-dependent apoptosis in salivary epithelial cells.
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Apoptose/fisiologia , Antígenos CD40/metabolismo , Células Epiteliais/patologia , NF-kappa B/metabolismo , Glândulas Salivares/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Western Blotting , Antígenos CD40/imunologia , Ligante de CD40/metabolismo , Ligante de CD40/farmacologia , Células Cultivadas , Fragmentação do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Células Epiteliais/química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Citometria de Fluxo , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/química , Fosforilação/efeitos dos fármacos , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Transdução de SinaisRESUMO
Objective To investigate the level of IL-17 and its clinical significance in patients with primary Sj(o)gren's syndrome (pSS) complicated with interstitial lung disease (ILD).Methods IL-17 levels were detected by enzyme linked immunosorbent assay (ELISA) in 53 untreated patients with pSS (25patients with only lacriminal and/or salivary gland involvement,28 with only interstitial lung disease involvement) and 15 healthy controls.The related clinical and laboratory data were recorded.ANOVA,LSDtest and Pearson test were used for statistical analysis.Results There were significant differences between the 3 groups(F=22.504,P=0.000).The mean concentration of sera IL-I7 in the patients with ILD was significantly higher than in patients with only lacriminal or salivary gland involvement (P<0.05).There was no difference in the levels of sera IL-17 between the patients with only lacriminal and/or salivary gland involvement and healthy controls (P>0.05).Conclusion Our results show that patients with pSS concomitant with ILD have high serum IL-17 levels,which highlight the role of IL-17 in Sj(o)gren's syndrome interstitial lung injury.
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Objective To better understand the clinical features and the diagnosis of acquired Gitelman syndrome associated with primary Sj(o)gren syndrome (SS).Methods Two cases of acquired Gitelman syndrome associated with primary SS were investigated.Literature were reviewed.Results Two women with sicca complex presented to our clinic with intermittent muscle cramping and weakness involving both lower extremities for several months.Laboratory findings showed hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria,all these met the criteria for Gitelman syndrome.Diagnostic evaluation identified primary SS as the cause of the acquired Gitelman syndrome.Conclusion Acquired Gitelman syndrome associated with SS is rare.Kidney biopsy is necessary for the diagnosis of Gitelman syndrome.Further studies are needed.
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Objective To evaluate the efficacy,safety and impact of recombinant human cytotoxic T lymphocyte-associated antigen (CTLA)-4 fusion proteins (rhCTLA-4Ig) on serum human tumor necrosis factor (TNF)-α and CX3CL1 in active rheumatoid arthritis (RA) patients.Methods Forty-four RA patients were treated with rhCTLA-4Ig and placebo.Clinical response was assessed by American College of Rheumatology (ACR) criteria and disease activity score in 28 joints (DAS28).The levels of serum TNF-α and CX3CL1 were determined in 44 RA patients and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA).Comparisons between groups were performed by t-test or x2 test.Results At week 12,ACR20,ACR50and ACR70 responses in RA patients with rhCTLA-4Ig were achieved by 95%(20/21 ),76%( 16/21 )and 19%(4/21) respectively,but no patient with placebo achieved ACR20,ACRS0 and ACR70 responses.There were significantly statistical differences in ACR20 and ACR50 responses (x2=39.17,26.69,P<0.01 ).At week 12,the mean DAS28 in the rhCTLA4Ig group was 3.1±1.3 versus 6.2±1.1 at baseline (P<0.01).Similarly,health assessment questionnaire (HAQ) improved significantly,declining from 1.4±0.5 at baseline to 0.4±0.5 at week 12 (P<0.01).However,the mean DAS28 in the placebo group was 5.8±1.2 versus 6.0±0.7 at baseline (P>0.05),HAQ declined from 1.6±0.4 to 1.6±0.6 (P>0.05).In addition,there were higher levels of TNF-α and CX3CL1 in the active RA patients than those of the healthy controls (P<0.01).After 12 weeks therapy,Serum TNF-α and CX3CL1 levels in the rhCTLA-4Ig group decreased significantly (P<0.01).There weren't decline in the placebo group (P>0.05).Conclusion This study has shown that rhCTLA-4Ig is very effective in reducing disease activity,improving function during the 12 weeks treatment.rhCTLA-4Ig therapy for 12 weeks can lead to significant decrease of serum TNF-α and CX3CL1.
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Objective To explore the effect of the JAK/STAT signal pathway on the apoptosis-related gene in the synovial tissue of rat rheumatoid arthritis (RA).Methods Fifty rat models of collagen-induced arthritis,whose arthritis index was more than 2,were divided into the model group,the low dose of AG490 group,the medium dose of AG490 group and the high dose of AG490 group.In addition,6 rats were treated intraperitoneal injection.Then,the arthritis index and the change of apoptosis-related genes were compared.Multiple-sample average was analyzed by single-factor x2 test and LSD-t or Tamhane's T 2 test were used for two-two comparison.Results The arthritis index of the model group increased evidently,and the apoptosis inhibitor Bcl-2,Bcl-xl gene and protein expression was up-regulated,which was significantly different when compared with that of the control group(0.931±0.035 vs 0.351±0.024,0.920±0.037 vs 0.271±0.029,0.322±0.047 vs 0.230±0.031 ).The expression of apoptosis promoting factor Bax wasslightly up-regulated.The blockage of JAK/STAT pathway cotld down-regulate the expression levels of the gene and protein of survivins Bcl-2 and Bcl-xl,and up-regulate the gene and protein expressions of Bax.Conclusion In the process of RA development,apoptosis inhibitor Bcl-2,Bcl-xl gene and protein expression is up-regulated.JAK/STAT signal transduction pathway regulates the apoptosis process.
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Objective To compare and analyze the different clinical features between male and female patients with rheumatoid arthritis (RA), by detecting the gender difference to make clinical decisions. Method The clinical features of 95 male RA patients(MRA) were analyzed and compared with those of 248 female RA patients (FRA) by retrospective analysis method. Results The mean onset age of MRA [18-79 (51.40±15.55) years old] was older than that of FRA[18-75(43.54 ±15.46) years old](P=0.0002). The morning stiffness time of MRA [(1.58 ±1.34) h] was shorter than that of FRA [(2.10 ±1.51) h](P = 0.0357). There was statistical difference in the first involved joint between MRA and FRA (P=0.0170), the prevalence of knee,metatarsonphalangeal joint,shoulder and ankle of MRA was higher than those of FRA, ' but conversely the wrist prevalence of FRA was higher than that of MRA.The prevalence of secondary Sj(o)gren syndrome of MRA(13.68%, 13/95) was rather lower than that of FRA(35.08%, 87/248)(P = 0.0007). MRA had lower positive rate of ANA (2.11% ,2/95) and lower value of IgM [(1.42 ±0.75) g/L] than FRA [(10.48% ,26/248), (1.69 ±0.86) g/L] (P 0.05). Conclusions MRA patients have older onset age and milder articular symptom than FRA patients. The disease severity of MRA is similar to that of FRA. Weighted joints are more involved in MRA. FRA is more inclined to have secondary Sj(o)gren syndrome.
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Objective To investigate the clinical significance of serum interferon-λ1(IFN-λ1) levels in patients with systemic lupus erythematosus(SLE).Methods ELBA was used to evaluate the serum level of interferon-λ1 in 60 patients with SLE and 20 healthy individuals as normal control.SPSS10.0 statistic software was employed to investigate the relation between the serum IFN-λ1 level,the laboratory index and SLE disease activity index(SLEDAI).Results The serum IFN-λ1 level in SLE patients(74.2±16.1 pg/ml) was higher than that of the normal controls(70.4±12.6 pg/ml,P=0.339).The serum IFN-λ1 level in SLE patients with leucopenia(80.1±18.1 pg/ml) was higher than those of the normal control(P=0.052) and the SLE patients without leucopenia(70.6±13.7 pg/ml,P=0.024).The serum IFN-λ1 level was not correlated with SLEDAI,complements C3,C4,24-hour-proteinuria.Conclusion IFN-λ1 may be involved in the pathogenesis of leukopenia in SLE and it has not been proved that its level was correlated with the disease activity.
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Objective To study the expression of thymus and activation-regulated chemokine(TARC)in the kidney of MRL/lpr mice and to elucidate the molecular pathogenesis of lupus nephritis.Methods The 24-hour urine protein of 4 MRL/lpr mice of 16 weeks of age and 4 age-and sex-matched BALB/c mice was measured.The expressions of TARC mRNA and protein in the kidneys of MRL/lpr mice and BALB/c mice were detected by reverse transcription polymerase chain reaction and Western blot,respectively.Results The 24-hour urine protein and the expression level of TARC mRNA were significantly higher in MRL/lpr mice than in BALB/c mice(P<0.05).The expression of TARC protein was detectable only in MRL/lpr mice.Conclusion The expression of TARC increases in the kidney of mice with systemic lupus erythematosus,suggesting that TARC may be involved in lupus nephritis in mice.
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Objective To discuss the role of p38MAPK signal pathway in the process of TWEAK inducing rheumatoid arthritis(RA) fibroblast-like synoviocyte(FLS) to synthesize MMP-9 and look for a new target for RA treatment. Methods RA FLS were primarily cultured and stimulated with TWEAK. Western blot was used to detect the expression of p-p38MAPK and p65 in RA FLS. FLS were pretreated by SB203580 or not. ELISA was used to detect the concentration of MMP-9 in cell-cultured fluid. The mRNA expression of MMP-9 was measured by RT-PCR. Results TWEAK( 100 ng/ml) can make p38MAPK phosphorylated and increased the expression of p65 protein in the cell nucleus. SB203580 can partially inhibit the expression of MMP-9 and MMP-9 mRNA produced by RA FLS which is induced by TWEAK. Conclusion TWEAK induced RA FLS to synthesize MMP-9, in that process, the p38MAPK signal trausduction pathway was in active state, and induced the expression of NF-κB.
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Objective To study whether p38 mitogen-activated protein kinases (p38MAPK) signal pathway were activated in the process of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) which then induces rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) to synthesize matrix metalloproteinase-1 (MMP-1) and look for the relative mechanisms of how TWEAK was involved in the destruction of articular bones and cartilage. Methods RA FLS were primarily cultured and stimulated with TWEAK. FLS were pretreated with SB203580 or not. ELISA was used to detect the concentration of MMP-1 in cell-cultured supernatant. Western blotting was used to detect the expression of p-p38MAPK and P65 in RA FLS. Results TWEAK (100 ng/ml) could induce RA FIS to synthesize MMP-1. SB203580 could partially inhibite the expression of MMP-1 producted by RA FLS which was induced by TWEAK. TWEAK could make p38MAPK phosphorylated and increase the expression of P65 protein in the cell nucleus. Conclusion TWEAK induces RA FLS to synthesize MMP-1. In this process, p38MAPK signal transduction pathway is activated and then induce the expression of NF-κB.
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Objective To investigate the effect of T lymphocyte proliferation,Th1 and Th2 cytokines on T cells from systemic lupus erythematosus (SLE)patients by blocking 4-1BB/4-1BBL.Methods The proliferation of T cells from 30 SLE patients and 20 normal controls was detected by MTT and the levels of patients stimulated with anti-CD3 McAb were significantly higher than those of T cells without stimulation(P<IFN-γand IL-4 in SLE were significantly higher than those of normal controls(P<0.01).There were more ex-pression of IFN-γ and IL-4 in supernatant of T cells from SLE after stimulated with anti-CD3 McAb(P<0.01).However,the production of IFN-γ and IL-4 was inhibited by anti-4-1BB McAb(P<O.05),and especially the level of IL-4 was markedly decreased.Conclusion Blocking 4-1BB/4-IBBL can significantlv inhibit the abnormal activation of T cells and the secretion of Thl and Th2 cytokines of SLE.
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Objective To investigate the effect of costimulatory molecules 4-1BB/4-1BBL on T cell activation with systemic lupus erythematosus(SLE)patients.Methods The expression of NF-kB mRNA and p38 MAPK mRNA of T cells with 20 SLE patients and 20 normal controls before activation,after activation and blocked bv 4-1BB/4-1BBL were detected bv RT-PCR.The protein levels of p-p38 MAPK and NF-kB were detected by Western blot.Results The expression of NF-kB mRNA and p38 MAPK mRNA and the protein expression of NF-kB and p-p38 MAPK of T cell with SLE patients were higher than that of normal controls(P<0.01).There were more expression of NF-kB mRNA,p38 MAPK mRNA,NF-kB protein and p-p38 MAPK protein of T cell with SLE patients stimulated by anti-CD3 monoantibody(P<0.01).In anti-4-1BB monoantibody blockage group,there were decreased expression of p38 MAPK mRNA and p-p38 MAPK protein(P<0.01).but not the decreased NF-kB mRNA and protein expression.Conclusion Costimulatory molecule 4-1BB plays a critical role in T cell activation of SLE by p38 MAPK signal pathway.
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Objective:To investigate the inductive function of tumor necrosis factor(TNF)-? to dentritic cell(DC) and its effect on erythroid hematopoiesis.Methods:Human CD34~+ cells was separated and purified by MACS method.With the existence of stem cell factor(SCF),interleukin-3(IL-3) and erythropoietin(EPO),CD34~+ cells were cultured together with TNF-? through external fluid.The expanding times of cells and their superficial markings were analysed by flow cytometry.Meanwhile,the morphological transformation of expanding cells was observed by microscope.Results:TNF-? could inhibit the development of glycophorin A(GPA;a specific erythroid marker) positive cells,while stimulates the growth of those GPA negative of non-erythroid cells.These cells usually possess the morphological characteristic of DCs and express phenotypical markers of DCs accordingly.Those erythroid progenitor cells which contact directly with DCs appear to have the change of cellular apoptosis.Conclusion:The inhibition of TNF-? to erythroid hematopoiesis is probably related to the induction of DCs proliferation.The possible reason for cellular apoptosis of erythoid progenitor cells may be their direct contact with DCs.