OBJECTIVETo investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients.

METHODSFifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls. PBMC were obtained by Ficoll density gradient centrifugation. IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cultured PBMC of LN patients or normal controls. IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSIn medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492.1 +/- 73.2 ng/ml vs 636.7 +/- 51.9 ng/ml for IgG, 306.6 +/- 53.7 IU/ml vs 95.8 +/- 11.6 IU/ml for anti-dsDNA and 50.92 +/- 15.92 ng/ml vs 1.77 +/- 0.73 ng/ml for IL-6, all P < 0.001). In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher. The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG(28) and partially blocked by dexamethasone. Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent. During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1.80 +/- 0.11 vs 0.36 +/- 0.07). During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3.21 +/- 0.24 vs 1.30 +/- 0.14, P < 0.05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control.

CONCLUSIONSIL-17 may play an important role in the pathogenesis of LN through the induction of IgG, anti-dsDNA overproduction and IL-6 overexpression of PBMC in LN patients.

Adolescent ; Adult ; Antibodies, Antinuclear ; biosynthesis ; Autoantibodies ; biosynthesis ; Female ; Humans ; Immunoglobulin G ; biosynthesis ; Interleukin-17 ; pharmacology ; Interleukin-6 ; biosynthesis ; genetics ; Leukocytes, Mononuclear ; metabolism ; Lupus Nephritis ; immunology ; Male ; RNA, Messenger ; analysis

OBJECTIVETo determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).

METHODSPeripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated STAT3 and STAT4 signaling molecules in PBMCs were detected by immunoblot.

RESULTSLevels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA ) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of STAT3 and STAT4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated STAT3 and STAT4 might be observed in normal PBMCs treated with IL-12 plus PHA.

CONCLUSIONIL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated STAT3 and STAT4 signaling molecules.

Adolescent ; Adult ; Cells, Cultured ; DNA-Binding Proteins ; metabolism ; Humans ; Interleukin-12 ; blood ; genetics ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; metabolism ; Middle Aged ; Phosphorylation ; RNA, Messenger ; analysis ; STAT3 Transcription Factor ; STAT4 Transcription Factor ; Trans-Activators ; metabolism

AIM:To determine whether human peritoneal mesothelial cells express CD40. METHODS:Human peritoneal mesothelial cells (HPMC) were harvested from spent peritoneal dialysis effluent and maintained under defined in vitro conditions. Expression of CD40, CD40L and intercellular adhesion molecule-1 (ICAM-1) on HPMC under normal culture or stimulation with interferon-γ (IFN-γ), tumor necrosis factor-α(TNF-α), interleukin(IL)-1 and LPS were detected by FACS analysis. The relationship between CD40 expression and ICAM-1 expression on HPMC was analyzed.RESULTS:HPMC cultured in vitro expressed CD40 constitutively. The surface expression of CD40 was markedly up-regulated following stimulation with IFN-γ, but not with TNF-α, IL-1 and LPS. CD40L expression on HPMC was not detected. The expression of ICAM-1 on HPMC was significantly increased by stimulation with IFN-γ, TNF-α, IL-1, LPS, respectively; the most effective inducer on ICAM-1 expression was IFN-γ. The CD40 expression co-localizes with the expression of ICAM-1 and there was positive correlation between CD40 and ICAM-1 expression on HPMC. CONCLUSION:HPMC functionally expressed CD40.

AIM:To investigate the regulatory role of nuclear factor κB (NF-κB) in the expression of interleukin-6 in mesangial cells (MC) induced by interleukin-1β.METHODS:Activation of NF-κB was measured by electrophoresis mobility shift assay (EMSA). RT/PCR and ELISA were used to detect IL-6 mRNA expression and IL-6 production, respectively.RESULTS:rhIL-1β could rapidly stimulate the activation of NF-κB in MC, and increase the expression of IL-6 mRNA and protein. PDTC, one of the inhibitor of NF-κB， could inhibit the expression of IL-6 in mRNA and protein in MC stimulated by rhIL-1β.CONCLUSION:IL-6 expression induced by IL-1β may be regulated by NF-κB in MC, NF-κB may modulate the immune-inflammatory reaction in glomerular disease.

【Objective】To observe the expression of PI3-K phosphorylated products and elucidate the correlation between PI3-K phosphorylated products and Th2 cytokine in peripheral blood mononuclear cell (PBMC).【Methods】14 patients with active lupus nephritis and 12 controls were selected,PI3-K phosphorylated products were detected by immunoprecipitation and Western blotting,RT-PCR was used to observe interleukin-6 mRNA and interleukin-10 mRNA expression.【Results】In either spontaneous condition or stimulated by anti-CD3 antibody,the expression of PI3-K phosphorylated products in patients with active lupus nephritis were higher than those of the controls(1.14±0.23 vs 0.46±(0.12，P=0.023;2.09±0.63 vs 0.65±0.14，P=0.016).The expression of PI3-K phosphorylated products in active lupus nephritis showed a positive correlation with interleukin-6 mRNA and interleukin-10 mRNA (r=0.652,P=0.008;r=0.718,P=0.007).PY294002,one of specific inhibitor of PI3-K,inhibited significantly the expression of interleukin-6 mRNA(2.32±0.51 vs 0.57±0.15,P=0.009) and interleukin-10 mRNA (1.71±0.33 vs 0.67±0.11,P=0.006) in stimulated PBMC in active lupus nephritis.【Conclusion】PI3-K can involve in the pathogenesis of lupus nephritis by inducing the overexpression of interleukin-6 and interleukin-10.

Objective To study clinical feature,pathology,treatment and outcome of acute renal failure(ARF) in idiopathic nephrotic syndrome(IDNS).Methods History-taking of 38 cases were carried out all detailly 24-hour urine protein,biochemistry markers,hemorheology,renal histopathology were detected.Results The study fandings that 82 percent of patients were less than 40 years old,76 3 percent were male,74 percent(28 patients) were non-oliguria and 52 6 percent were minimal change glomerulonephritis through the renipuncture,most of the cases had edema of interstitium, by give prednisone of standard dosage,symptomatic treatment or dialysis the satisfying efficacy was got.Conclusions The main features of IDNS complicated with ARF are usual,it is non-oliguria type in clinic minimal glomerulonephritis in pathology,and deficient blood volume leads to occurrence of ARF,but the renal function could be recovered by give prednisone of routine dosage,symptomatic treatment and hemodialysis therapy.

0 05).Of patients with lupus renal lesions 86% had a positive LBT (+LBT),which was significantly higher than that of patients without renal lesions(37%) ( P

Objective To investigate the value of dialysis and ethics of withdrawal dialysis.Method Through analysis of some typical cases of ESRD patients,to investigate the value of dialysis.Conclusion A lot of ESRD patients can survive through dialysis,thanks to the improvement of medical science in last 30 years.On the other hand,it can also keep some patients with no living calculation surviving,becoming the burdensome of families,hospitals and societies.Our object is to discuss the ethics of withdrawal dialysis in our country.

ObjectiveTo investigate the clinical features of acute myocardial infarction in CAPD patients.MethodsCompare the clinical and laboratory data of 39 patients with CAPD and AMI for the first time (PD group),including clinical symptoms,signs,electrocardiogram changes,myocardial enzyme changes and in hospital mortality,with those of 50 patients without renal insufficient but with AMI for the first time (C group).Diagnosis of AMI was made in hospital.ResultsCompared to C group, the symptoms presented at first in PD group were more atypical and the patients went to see doctor more lately after AMI.Atypical electrocardiogram changes were more in PD group than in C group (61.5% vs 26.0%,P

Objective:To detect the activation of NF AT and AP 1 in peripheral blood mononuclear cells(PBMCs) in patients with systemic lupus erythematosus and investigate their relationship with serum ANA,anti dsDNA antibody,ESR,CRP and C 3.Methods:Activation of NF AT and AP 1 were detected by electrophoretic mobility shift assay(EMSA).Results:①Activation of NF AT in PBMC in active and inactive SLE patients was increased when compared with normal controls,respectively,and the activation of NF AT in active patients was higher than that of inactive ones.②Elevated activation of AP 1 in PBMC in active SLE patients was found as compared with normal controls,and there was no significant difference in activation of AP 1 between inactive patients and normal control.③Activation of NF AT in SLE patients with positive anti dsDNA antibody was higher than that of patients with negative anti dsDNA antibody,and there was not different positively in AP 1 activation between above two patient groups.④Activation of NF AT in PBMC was related positively with CRP and SLEDAI,respectively,but no correlation with ESR,ANA,C 3.There was no relation between the activation of AP 1 and above clinical parameters.Conclusion:The abnormal expression of NF AT and AP 1 indicates disturbed intracellular signaling in SLE,which is suggested that alternations in activation of transcription factors may contribute to the pathogenesis of SLE.Activation of NF AT may be used as a predicator of SLE disease activity.