Search

OBJECTIVE To investigate the expression and regulation of human β-defensin-2 (HBD-2) in the prostate. PATIENTS AND METHODS Normal human prostate epithelial cell line (RWPE-1), human prostate cancer cell lines (DU-145, PC-3), and paraffin-embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT-PCR and immunohistochemical staining. HBD-2 expression was also analysed by RT-PCR and ELISA in RWPE-1 cells treated with lipopolysaccharide (LPS). Nuclear factor-κB (NF-κB) activation was assessed by IκBα immunoblotting and electrophoretic mobility shift assay (EMSA). RESULTS BPH tissue and all of the tested prostate cell lines other than PC-3 constitutively express HBD-2 mRNA. HBD-2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages. Exposure to LPS induced HBD-2 upregulation and NF-κB activation, as assessed by IκBα phosphorylation and degradation in RWPE-1 cells. Bay11-7082, an NF-κB inhibitor prevented LPS-induced HBD-2 production in RWPE-1 cells. CONCLUSIONS Prostate epithelial cells may constitutively express HBD-2, and its expression was upregulated by LPS. Our data indicate that HBD-2 may be an important immunomodulatory factor in prostate function. Expression of HBD-2 in normal prostates and the potential role of HBD-2 in prostatitis and BPH should be addressed in the future. [ABSTRACT FROM AUTHOR]

The apoptotic effect of fluoxetine (FLX), an antidepressant, against human epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in relation to the mitochondria-mediated cell death process and nuclear factor (NF)-κB activation. FLX-induced mitochondrial membrane permeability change and formation of reactive oxygen species, leading to cell death. FLX-induced increase in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of the mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an inhibitor of nuclear factor kappaB (NF-κB) activation] prevented the FLX-induced cell death, increase in phosphorylated inhibitory κB-α and NF-κB p65 levels, and binding of NF-κB p65 to DNA. Results from this study suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines by inducing the mitochondrial membrane permeability change, which leads to cytochrome c release and subsequent caspase-3 activation, through reactive oxygen species-dependent activation of NF-κB. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the effect of endothelin-1 (ET-1) on the production of interleukin-6 (IL-6) in cultured human detrusor smooth muscle cells (HDSMCs) and the effect of IL-6 on the contractile response of bladder smooth muscle strips from rats. MATERIALS AND METHODS The expression of IL-6 mRNA and production of IL-6 protein in cultured HDSMCs treated with the different concentrations of ET-1 were assayed by reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay, respectively. The strips from Sprague-Dawley rats were either untreated or treated with 1 ng/mL of IL-6 for 60 min. Using increasing cumulative concentrations of acetylcholine (ACh), bethanechol (BCh), or sodium nitroprusside, we assessed the concentration-contraction or the relaxation responses. In cystitis-induced strips, change of contractions induced by noradrenaline (NA) with or without treatment of IL-6 were assessed. The IL-6-treated strips were incubated for 30 min in the presence or absence indomethacin or SQ29548, and then the effects on ACh- or BCh-induced contractions were measured. RESULTS The expression of IL-6 mRNA and the production of IL-6 protein on the cultured HDSMCs pretreated by ET-1 were significantly higher than in the control ( P < 0.05). The ACh- and BCh-induced contractions were increased in the IL-6 pretreated strips from both dome and trigone, regardless of the presence of urothelium ( P < 0.05). The presence of cystitis augmented the NA-induced contractions ( P < 0.05). The contractions induced by ACh and BCh were inhibited by indomethacin and SQ29548. CONCLUSIONS ET-1 induces expression of IL-6 mRNA and production of IL-6 protein on HDSMCs. IL-6 enhances detrusor smooth muscle contractility via the muscarinic or adrenergic receptor pathway. [ABSTRACT FROM AUTHOR]

Aim: We performed a retrospective study to examine the association between the metabolic syndrome (MS) and risk for the development of chronic kidney disease (CKD). Methods: This cohort study included 60 921 healthy adults recruited from two health promotion centres. Anthropometric measures, blood pressure, fasting glucose, lipid profile and serum creatinine were evaluated. The glomerular filtration rate was estimated (eGFR) using the abbreviated equation developed by the Modification of Diet in Renal Disease (MDRD) formula. CKD was defined as an eGFR of <60 mL/min per 1.73 m2 or the presence of proteinuria. Results: The prevalence of MS and CKD was 19.0% and 7.2% respectively. Those with MS had a higher prevalence of CKD (11.0% vs 6.3%, P < 0.001) than those without MS. As the number of MS components increased, the prevalence of CKD increased and the eGFR decreased. The multiple linear analyses showed that each of the components of the MS was negatively correlated with the eGFR. Unadjusted and multivariate adjusted associations were identified between MS and CKD. Individuals with MS had a multivariate adjusted odds ratio of 1.680 (95% confidence interval, 0.566–1.801) for CKD compared with those without MS. Conclusion: Our findings, which were obtained from a large Korean cohort, suggest that MS was associated with CKD. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the association between serum prostate-specific antigen (PSA) level and age, liver function tests (LFTs) including alkaline phosphatase (ALP), total bilirubin (TB), lipid profile (total cholesterol, TC, triglycerides, TG, high-density lipoprotein, HDL) and fasting blood sugar (FBS), and to determine the significant factors for predicting the serum PSA level in men with a low risk of having prostate cancer. SUBJECTS AND METHODS In all, 38 157 healthy male employees of the Korea Electric Power Corporation (KEPCO) who were aged <60 years and had serum PSA levels of <4 ng/mL and serum creatinine levels of <1.4 mg/dL were enrolled between January 2002 and December 2006. Body weight and height were measured, and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, TB, FBS, TC, TG, and HDL, and serum PSA were measured. RESULTS The mean (sd) age of the study population was 44.4 (7.90) years and the mean PSA level 0.89 (0.51) ng/mL. In a univariate analysis there were significant interrelations between serum PSA level and age, BMI, AST, ALT, ALP, TB, HDL and FBS ( P < 0.05). The multiple logistic regression analyses using four percentiles (10th, 25th, 75th, 90th percentile) of serum PSA level showed trends that being older was associated with serum PSA level, and that BMI, ALT, HDL and FBS were negatively correlated with serum PSA level. CONCLUSIONS These results suggest that serum PSA level was significantly influenced by age, BMI, ALT, HDL and FBS. Further studies are needed to confirm our results and to explain the underlying mechanisms. [ABSTRACT FROM AUTHOR]