BACKGROUND: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. METHODS: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 (AT1) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [3H]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. RESULTS: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the AT1 receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an AT1 receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. CONCLUSION: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.
Angiotensin II ; Animals ; Arachidonate 12-Lipoxygenase ; Blotting, Western ; Contracts ; DNA ; Flavanones ; MAP Kinase Signaling System ; Muscle, Smooth, Vascular ; Rats ; Rats, Inbred SHR ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

BACKGROUND: 15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. METHODS: Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-kappaB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. RESULTS: 15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPAR gamma, and dependent on NF-kappaB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS. CONCLUSION: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPAR gamma and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.
Blotting, Western ; Electrophoretic Mobility Shift Assay ; Flow Cytometry ; MAP Kinase Signaling System ; Muscle, Smooth, Vascular ; NADPH Oxidase ; NF-kappa B ; Phosphorylation ; PPAR gamma ; Prostaglandin D2 ; Rats, Inbred SHR ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

Interferon-gamma (IFN-gamma) is well known as a potent inducer in monokine induced by IFN-gamma (Mig) mRNA expression. Although lipopolysaccharide (LPS) alone is weakly effective on Mig mRNA expression. the stimulation of LPS and IFN-gamma (LPS/IFN-gamma simultaneously has been shown to synergize to produce a high level of Mig mRNA in mouse peritoneal macrophages. In this study, interleukin-10 (IL-10) was found to suppress the LPS/IFN-gamma- induced Mig mRNA expression in cell type- and mouse strain-specific fashion, but IFN-gamma alone-induced Mig mRNA was unaffected by IL-10 under identical experimental conditions. The IL-10-mediated suppression of LPS/IFN-gamma-stimulated Mig mRNA expression was dependent on the concentration of IL-10, and was prevented when the agent was added 2 hours after LPS/IFN-gamma treatment. The suppressive action of IL-10 was dependent on a protein synthesis. However, IL-10 did not reduce the stability of LPS/IFN-gamma-induced Mig mRNA. These data may have important implications for a previously unrecognized role for IL-10 as a regulator of synergistic effect of LPS on the IFN-gamma-induced expression of the Mig gene in macrophages.
Animals ; Gene Expression* ; Interferon-gamma ; Interleukin-10* ; Macrophages ; Macrophages, Peritoneal ; Mice ; RNA, Messenger

This study was to investigate clinical characteristics and any differential trends in survival among renal replacement therapy (hemodialysis [HD], peritoneal dialysis [PD], and kidney transplantation [KT]) in Korean end-stage renal disease (ESRD) population. We tried to analyze retrospectively the survival rate adjusted by risk factors and the relative risk stratified by key risk factors among 447 ESRD patients who began dialysis or had a kidney transplant at Ajou University Hospital from 1994 to 2004. In adjusted Cox survival curves, the KT patients had the best survival rate, and the HD patients had better survival than PD patients. The consistent trends in different subgroups stratified by age and diabetes were as following: 1) The risk of death for PD and HD was not proportional over time, 2) The relative risk of PD was similar or lower than that of HD for the first 12 months, but it became higher at later period. The significant predictors for mortality were age (over 55 yr), presence of diabetes, cerebrovascular accident at ESRD onset, and more than one time of hospitalization caused by malnutrition. Further large-scaled, multicenter-based comparative study is needed in Korean ESRD patients and more meticulous attention is required in high-risk patients.
Survival Analysis ; Renal Replacement Therapy/*mortality ; Morbidity ; Middle Aged ; Male ; Kidney Transplantation ; Kidney Failure, Chronic/*mortality ; Humans ; Follow-Up Studies ; Female ; Aged ; Adult

Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 (AT2) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the AT2 receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an AT2 receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the AT2 receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.
Angiotensin II ; Angiotensins ; Arachidonate 12-Lipoxygenase ; Cell Proliferation ; Chemokine CCL5 ; Down-Regulation ; Hypertension ; Muscle, Smooth, Vascular ; Phosphorylation ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 2 ; RNA, Messenger

BACKGOUND: The progression rate of IgA nephropathy is known to be variable. We tried to draw an equation that can predict the interval till end stage renal disease (ESRD). METHODS: We retrospectively checked the risk factors of the progression such as demographic, clinical, laboratory, and histologic data by using simple linear regression in eighty eight (M:F=53:35) patients with biopsy-proven IgA nephropathy from Oct 1994 to Aug 2004. By multiple linear regression, a semiquantitative equation estimating the rate of progression was developed. We also evaluated whether there is a "point of no return" that progresses to ESRD which was shown by D'Amico ('93) and Scholl ('99) by receiver operating characteristic (ROC) curve analysis. RESULTS: Mean age and follow-up period were 34.1+/-13.6 years and 55.7+/-31.4 months. Among the risk factors, spot urine protein to creatinine ratio and mean arterial pressure during the follow-up period were significantly associated with the rate of progression (p<0.05). A semiquantitative equation estimating the rate of progression using the two factors was developed as follow. (delta)CCr=2.206-(0.128 x PCR(follow-up))-(0.023 x MAP(follow-up)) (MAPfollow-up:mean arterial pressure; regression coefficient=-0.023, PCRfollow-up:spot urine protein/creatinine; regression coefficient=-0.128). By ROC curve analysis, all patients with maximum serum creatinine over 4.1 mg/ dL during follow-up were found to progress to ESRD. CONCLUSION: We conclude that in Korean IgA nephropathy patients we could predict the rate of decline in renal function for individual patients semiquantitatively and we could confirm the existence of a "point of no return" during the course of IgA nephropathy.
Arterial Pressure ; Creatinine ; Follow-Up Studies ; Glomerulonephritis, IGA* ; Humans ; Immunoglobulin A* ; Kidney Failure, Chronic ; Linear Models ; Retrospective Studies ; Risk Factors ; ROC Curve

BACKGROUND: The question of which dialysis modality should be recommended to end-stage renal disease (ESRD) patients with a history of coronary artery disease (CAD) is encountered frequently in clinical practice, and the answer is still controversial. We tried to explore the patient's survival difference by the dialysis modality in incident ESRD patients with CAD. METHODS: We retrospectively analyzed survival differences by dialysis modality in 56 new ESRD patients with preexisting CAD (HD: PD=30: 26) at yearly intervals with Poisson regression from September 1994 to February 2000. We also investigated the predictors of mortality with multivariate analysis by time-dependent Cox regression. RESULTS: There were no significant differences in age, sex, diabetes, co-morbidity, severity of CAD on commencement of dialysis between HD and PD patients with CAD. Cardiovascular deaths were observed in only HD group. In the CAD group, the relative risk (RR) of mortality in HD patients was equal or higher than that in PD patients for the first 3 years, but RR became lower in HD patient after 3 years. The significant predictors of mortality in CAD group were age, diabetes, arrhythmia and history of cardiac arrest at the time of dialysis initiation. CONCLUSION: When we choose a dialysis modality in incident ESRD patient with preexisting CAD, we could consider an early survival benefit of PD over HD and integrated dialysis approach as a treatment option in this patient group. Further investigation including control group is needed to evaluate in the multicenter, large-scaled manner.
Arrhythmias, Cardiac ; Coronary Artery Disease* ; Coronary Vessels* ; Dialysis* ; Heart Arrest ; Humans ; Kidney Failure, Chronic* ; Mortality ; Multivariate Analysis ; Retrospective Studies

BACKGROUND: Diabetic nephropathy is the main cause of the end-stage renal disease in Korea. This study was performed to evaluate the progression pattern and risk factors of diabetic nephropathy in type 1 diabetes patients. METHODS: Total 64 patients who were registered in Ajou University Hospital since April 1994 till April 2004 were enrolled. We retrospectively analyzed the influence of systolic and diastolic blood pressure, serum creatinine, total cholesterol, albumin, HbA1c and urine albumin excretion on the rate of decline in creatinine clearance (CCr) by Cockcroft- Gault equation. RESULTS: The patients (27 males/37 females), aged 32.8+/-9.1 (mean+/-SD) years, with a mean duration of diabetes of 9.5+/-4.9 years, were followed more than 6 months. CCr were 113.0+/-20 mL/min/1.73m2 at diagnosis and a mean decrease rate was 3.8+/-3.6 mL/ min/1.73m2/year. Doubling time of serum creatinine was 13.1+/-3.2 year in patients who developed doubling of their creatinine (26.6%). Microalbuminuria and overt proteinuria developed at 8.1+/-2.5 year and at 11.4+/-1.5 year after the diagnosis of type 1 diabetes respectively. A mean decrease rate of CCr was 6.1+/-2.9 mL/min/1.73m2/year in patients who develop ESRD after 14.2+/-2.8 years. During the follow up, systolic and diastolic blood pressure, serum total cholesterol were significantly higher and the mean serum albumin and creatinine clearance were significantly lower in chronic renal failure (CRF) group compared to non-renal failure (non-CRF) group (p< 0.05). There was no significant difference in HbA1c between CRF and non-CRF groups. CONCLUSION: The results may suggest that Korean type 1 diabetes patients with diabetic nephropathy in Ajou hospital have a rather faster decline in kidney function compared with other reports. But we need further prospective study to confirm this findings.
Blood Pressure ; Cholesterol ; Creatinine ; Diabetes Mellitus, Type 1 ; Diabetic Nephropathies* ; Diagnosis ; Follow-Up Studies ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea* ; Proteinuria ; Retrospective Studies ; Risk Factors ; Serum Albumin

Background and Objectives: To evaluate the impact of smoking in young adults on the risk of cardiovascular disease (CVD) and the clustering effect of behavioral risk factors such as smoking, obesity, and depression. Methods: A Korean nationwide population-based cohort of a total of 3,280,826 participants aged 20–39 years old who underwent 2 consecutive health examinations were included. They were followed up until the date of CVD (myocardial infarction [MI] or stroke), or December 2018 (median, 6 years). Results: Current smoking, early age of smoking initiation, and smoking intensity were associated with an increased risk of CVD incidence. Even after quitting smoking, the risk of MI was still high in quitters compared with non-smokers. Cigarette smoking, obesity, and depression were independently associated with a 1.3–1.7 times increased risk of CVD, and clustering of 2 or more of these behavioral risk factors was associated with a 2–3 times increased risk of CVD in young adults. Conclusions In young adults, cigarette smoking was associated with the risk of CVD, and the clustering of 2 or more behavioral risk factors showed an additive risk of CVD.