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Byung Kee Bang

Publications and source records attributed to Byung Kee Bang.

At least 19 recordsLinked to original sources
PubMed2006

The impact of intima-media thickness of radial artery on early failure of radiocephalic arteriovenous fistula in hemodialysis patients.

This study was performed to investigate the impact of intima-media thickness (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing radiocephalic AVF operation were included in this study. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. And then AVF patency was followed up for 1 yr after the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within 1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in patent group (n=59) (486+/-130 micrometer vs. 398+/-130 micrometer, p=0.004). The AVF patency rate within 1 yr after the operation was lower in patients with IMT > or = 500 micrometer (n=26) than in patients with IMT <500 micrometer (n=64) (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to be independent risk factor but not statistically significant. Our data suggest that increased radial artery IMT is closely associated with early failure of radiocephalic AVF in HD patients.

Adult↗
PubMed2005

Effect of FTY720 on chronic cyclosporine nephropathy in rats.

BACKGROUND: Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy. METHODS: Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II). RESULTS: FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment. CONCLUSIONS: FTY720 treatment prevents CsA-induced renal injury.

Angiotensin II↗
PubMed2005

Ultrasonographic measurement of intima-media thickness of radial artery in pre-dialysis uraemic patients: comparison with histological examination.

BACKGROUND: Increased intima-media thickness (IMT) of the radial artery is associated with early failure of radiocephalic arteriovenous fistula (AVF) in haemodialysis patients. Therefore, non-invasive measurements of radial artery IMT before AVF operations are very important in predicting AVF patency. This study was designed to evaluate the accuracy of high-resolution ultrasonography in measuring radial artery IMT in pre-dialysis uraemic patients. METHODS: This study enrolled 43 pre-dialysis uraemic patients awaiting radiocephalic AVF operations for the first time. In this study, 17 age- and sex-matched uncomplicated hypertensive patients and 15 healthy subjects were included as a control. We measured the internal diameter (ID) and IMT of the radial artery using high-resolution ultrasonography on the wrists of uraemic patients as well as the control group before the AVF operation. We obtained specimens of the radial artery during the AVF operation and directly measured the IMT by histological examination. RESULTS: The radial artery IMT of the uraemic patients (0.41 +/- 0.09 mm) was significantly thicker, compared to both those of the hypertensive (0.33 +/- 0.05 mm, P < 0.001) and the healthy patients (0.25 +/- 0.04 mm, P = 0.002). In contrast, the radial artery ID in the uraemic patients (1.85 +/- 0.48 mm) was smaller than both that of the hypertensive patients (2.08 +/- 0.31 mm, P = 0.023) and the healthy persons (2.34 +/- 0.37 mm, P = 0.001). Radial artery IMT had a negative correlation with radial artery ID in a total of 73 subjects (r = -0.290, P = 0.012). The value of the radial arterial IMT measured by sonographic examination correlated significantly with that by histological examination in 43 uraemic patients (r = 0.786, P < 0.001) and it correlated significantly with early AVF failure (r = 0.358, P = 0.027). CONCLUSION: Our data suggest that high-resolution ultrasonography is an effective tool in measuring radial artery IMT in uraemic patients before AVF operation.

Adult↗
PubMed2005

Calcitriol regresses cardiac hypertrophy and QT dispersion in secondary hyperparathyroidism on hemodialysis.

BACKGROUND: Sudden cardiac death is common in patients on hemodialysis (HD), and its rate is as high as 25% of all cardiac deaths associated with left ventricular hypertrophy (LVH) and secondary hyperparathyroidism. A prolonged QT interval on standard electrocardiography is related to an increase in sudden death in various patient groups. It is also well known that LVH has been noted in uremic patients with high parathyroid hormone levels. METHODS: To evaluate the response of intravenous calcitriol treatment on the QT interval and LVH in HD patients with secondary hyperparathyroidism (intact parathyroid hormone, iPTH, > 450 ng/ml), echocardiographic, electrocardiographic (ECG), and biochemical assessments were performed over a 15-week period in 25 HD patients before and after intravenous calcitriol treatment. We also evaluated 25 age-, sex-, HD duration-, and BMI-matched HD control patients with secondary hyperparathyroidism. RESULTS: In patients receiving intravenous calcitriol, a significant reduction in iPTH levels (p < 0.05) and alkaline phosphatase levels (p < 0.01) was found without changes in values of serum calcium and ionized Ca2+, phosphorus, Na+, K+, Mg2+, hematocrit, blood pressure, or other hemodynamic changes. Echocardiograms showed significant decreases in the thickness of the interventricular septum (p < 0.05), left posterior wall thickness (p < 0.05), and left ventricle mass index (LVMi, p < 0.01). In addition, sequential ECG measurement in patients with calcitriol treatment showed significant reductions in QTcmax (QTmax interval corrected for heart rates, p < 0.01) and QTc dispersion (QT dispersion corrected for heart rates, p < 0.01). However, in the control patients, biochemical, hemodynamic, and ECG changes, as well as myocardial structural and functional changes were not seen. Multiple regression analysis in all patients indicated that iPTH and LVMi levels were independent predictors of QTcmax while the LVMi level was the only independent predictor of QTc dispersion (p < 0.05). CONCLUSIONS: Our study showed a significant correlation between LVMi and QT dispersion in HD patients with secondary hyperparathyroidism. Intravenous calcitriol treatment, to be used for the control of secondary hyperparathyroidism, was found to cause regression of myocardial hypertrophy and a reduction in the QTc interval and dispersion, without biochemical and hemodynamic changes. These findings suggest that an active vitamin D metabolite has a cardioprotective action in HD patients.

Adult↗
PubMed2005

Persistent elevation of C-reactive protein may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.

BACKGROUND: C-reactive protein (CRP), which reflects chronic inflammation, is a strong predictor of cardiovascular mortality in hemodialysis patients. We investigated whether persistent elevation of CRP is associated with cardiac function and morphology in patients maintained on hemodialysis. METHODS: Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3 weeks in 52 stable hemodialysis patients, and echocardiographic studies were performed. RESULTS: 25 patients showed persistent elevation of predialysis hs-CRP (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01). Echocardiographic studies showed that left atrial diameter (LA, p < 0.05), interventricular septal thickness (IVST, p < 0.05), left ventricular end-diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p < 0.05) were higher in the high CRP group. However the ejection fraction (EF) was lower in the high CRP group (p < 0.05), which also contained more patients with low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute infection and type of vascular access between the groups. hs-CRP level was positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r = 0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the EF was negatively correlated with hs-CRP (r = -0.301, p < 0.05). In addition, the high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r = 0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = -0.311, p < 0.05). On multivariate analysis, the high CRP group (beta = -0.312, beta = 0.238, and beta = 0.318, respectively) was a significant predictor of EF (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01). CONCLUSIONS: Persistent elevation of CRP, which is an independent risk factor for EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.

Adult↗
PubMed2005

Preconditioning with 1,25-dihydroxyvitamin D3 protects against subsequent ischemia-reperfusion injury in the rat kidney.

BACKGROUND/AIM: Induction of heat shock protein 70 (HSP70) is important in the tolerance of subsequent ischemia-reperfusion (I/R) injury. The aim of this study was to evaluate the effect of HSP70 induction by 1,25-dihydroxyvitamin D3 (VD3) on subsequent I/R injury in rats. METHODS: HSP70 was induced in Sprague-Dawley rats by VD3 treatment for 7 days, and the effect of VD3 pretreatment on subsequent I/R injury was evaluated in terms of renal function, tubular necrosis score, tumor necrosis factor alpha mRNA expression, mitogen-activated protein kinase expression, and proliferating cell nuclear antigen expression. RESULTS: VD3 treatment increased HSP70 expression which was localized to renal tubular cells in the outer medulla. Pretreatment with VD3 before I/R injury resulted in (1) decreased blood urea nitrogen and serum creatinine levels; (2) decreased tubular cell necrosis; (3) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; (4) decreased tumor necrosis factor alpha mRNA expression, and (5) increased extracellular signal regulated protein kinase and decreased c-Jun N-terminal kinase expression. CONCLUSION: Our study demonstrates that VD3 is a nontoxic inducer of HSP70 and exerts a protective effect against subsequent I/R injury.

Animals↗
PubMed2005

Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.

BACKGROUND: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury. METHODS: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death. RESULTS: Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3). CONCLUSION: rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.

Animals↗
PubMed2005

Protective effect of peroxisome proliferator activated receptor gamma agonists on diabetic and non-diabetic renal diseases.

Peroxisome proliferator activated receptor gamma (PPARgamma) agonist has not only antidiabetic effect but also a protective effect against various types of injury of the kidney. The protective effects of PPARgamma agonists are observed in diabetic nephropathy and non-diabetic renal diseases such as 5/6 ablation model of renal failure, experimental glomerulonephritis, ischemia-reperfusion injury, hypertensive nephropathy and cyclosporin-induced renal injury. The mechanism of renoprotection by PPARgamma agonist is multifactorial. Anti-fibrotic and anti-inflammatory effects, suppression of renin-angiotensin system, vascular protective effect and antiapoptotic effect were proposed.

Animals↗
PubMed2005

Clinical significance of an early protocol biopsy in living-donor renal transplantation: ten-year experience at a single center.

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.

Acute Disease↗
PubMed2005

Blockade of angiotensin II with losartan attenuates transforming growth factor-beta1 inducible gene-h3 (betaig-h3) expression in a model of chronic cyclosporine nephrotoxicity.

BACKGROUND: We recently demonstrated that upregulation of the transforming growth factor (TGF)-beta1 inducible gene-h3 (betaig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between betaig-h3 expression and TIF during losartan treatment in this model. METHODS: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on betaig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-beta1 and intrarenal angiotensin II were compared across treatment groups. RESULTS: Concurrent administration of losartan significantly attenuated betaig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 +/- 5 vs. 39 +/- 5%, p < 0.01 vs. CsA) and the expression of TGF-beta1 mRNA (336 +/- 49 vs. 685 +/- 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 +/- 5 vs. 38 +/- 6, p < 0.05 vs. CsA). CONCLUSION: Losartan is capable of abrogating the upregulation of TGF-beta1 and betaig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Renal transplantation in a patient with idiopathic thrombocytopenic purpura.

The combination of idiopathic thrombocytopenic purpura (ITP) and chronic renal failure (CRF) is uncommon. This report highlights a case of renal transplantation in a patient with ITP. A 35-year-old man with ITP was admitted with uremic symptoms. A renal transplant and splenectomy was simultaneously performed. A prophylactic pneumococcous vaccination was performed and intravenous immunoglobulin (1 g/kg) was administered before and after the operation. The patient's platelet count increased gradually after the splenectomy. During a two-year follow up period, the graft function was well maintained. Renal transplantation in a patient with ITP is recommended with a well-designed strategy to prevent potential complications.

Adult↗
PubMed2005

Non-Hodgkin's lymphoma manifest as gingival hyperplasia in a renal transplant recipient.

Gingival hyperplasia is a frequent complication in transplant patients who receive cyclosporine or calcium channel blockers. We studied an unusual case involving a renal transplant recipient with post-transplant non-Hodgkin's lymphoma that manifested as gingival hyperplasia. We initially consider that it was a side effect of cyclosporine and nifedipine. The lesion did not respond to dose reductions or the withdrawal of cyclosporine and nifedipine, and the gingival hyperplasia progressed in a localized fashion, becoming ulcerated and bleeding easily. Histological examination revealed the presence of malignant lymphoma.

Adult↗
PubMed2004

Relations between eNOS Glu298Asp polymorphism and progression of diabetic nephropathy.

BACKGROUND: Nitric oxide (NO) is related to the pathogenesis of renal hemodynamics in diabetes mellitus. Endothelial nitric oxide synthase (eNOS) gene polymorphism is considered the deterioration factor for progressive renal disease. It has been reported that an interaction of angiotensin II (Ang II) and NO is involved in the control of glomerular hemodynamics. This study aimed to elucidate the roles of eNOS and the angiotensin-converting enzyme (ACE) gene polymorphism for the progression of type 2 diabetic nephropathy (DN). METHODS: Korean type 2 diabetic patients (n = 177) were studied. eNOS and ACE genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. They were divided into three groups: group 1 consisted of patients with normoalbuminruia (n = 59), group 2 had microalbuminuria (n = 35) and group 3 had overt nephropathy (n = 83). RESULTS: Group 3 had a higher frequency of eNOS(GT) than groups 1 and 2. Patients with eNOS(GT) genotype showed more rapid deterioration in renal function, higher incidence of overt nephropathy and lower renal survival than those with eNOS(GG) genotype. However, there was no significant association between the ACE genotypes and DN, and no interaction between eNOS and ACE gene polymorphism. CONCLUSION: These results imply that eNOS(GT) genotype is associated with the progression of type 2 DN in Korean patients.

Cohort Studies↗
PubMed2004

Expression of transforming growth factor-beta-inducible gene-h3 in normal and cyclosporine-treated rat kidney.

Up-regulation of transforming growth factor-beta (TGF-beta) is known to play an important role in the tubulointerstitial injury of chronic cyclosporin A (CsA) nephropathy, but the expression of the TGF-beta-inducible gene-h3 (betaig-h3) is undetermined. In this study we examined betaig-h3 expression and its relationship to tubulointerstitial injury in a rat model of chronic CsA nephropathy. Sprague-Dawley rats kept on a low-salt diet (0.05% sodium) were treated daily for 4 weeks with subcutaneous injections of vehicle (olive oil, 1 mL/kg) or CsA (15 mg/kg). The expression of betaig-h3 messenger RNA (mRNA) and protein was evaluated with the use of in situ hybridization, immunohistochemical methods, and immunoblotting. We also compared renal function, histologic findings (tubulointerstitial fibrosis), and expression of TGF-beta1 among treatment groups. In vehicle-treated kidney, betaig-h3 mRNA and protein were constitutively expressed in the outer medulla and cortex, which was confined to the terminal portion of afferent arterioles, the S3 segment of the proximal tubules, and distal convoluted tubules. CsA treatment significantly up-regulated betaig-h3 expression in the interstitium, especially in expanded and fibrotic areas. Quantitative analysis revealed that CsA induced a significant (twofold) increase in betaig-h3 mRNA and protein, and this increase was correlated with up-regulation of TGF-beta1 expression (r =.943, P <.001) and the tubulointerstitial fibrosis score (r =.746, P =.05). Our observations indicate that an increase in betaig-h3 expression, along with TGF-beta1 up-regulation, is closely associated with tubulointerstitial fibrosis in a rat model of chronic CsA nephropathy.

Animals↗
PubMed2003

Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy.

We investigated the effects of pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model of chronic cyclosporine A (CsA)-induced nephropathy. Sprague-Dawley rats were maintained on a low-salt diet (0.05% sodium) and treated daily for 1 or 4 wk with vehicle (olive oil; 1 ml/kg sc), CsA (15 mg/kg sc), or both CsA and pravastatin (5 or 20 mg/kg in the drinking water). Anti-inflammatory and antifibrotic effects of pravastatin were studied by evaluating the concentrations of the inflammatory mediators osteopontin (OPN) and C-reactive protein (CRP), of fibrotic cytokine-transforming growth factor (TGF)-beta1, and the presence of ED-1-positive cells (macrophages). In addition, renal function, serum lipid levels, histopathology (arteriolopathy and tubulointerstitial fibrosis), and the expression of the vasoactive factors endothelial nitric oxide synthase (eNOS) and renin protein were also compared for different treatment groups. Pravastatin induced dose-dependent decreases in the expression of OPN, intrarenal CRP, and TGF-beta1, and in the numbers of ED-1-positive cells at 1 and 4 wk. These were accompanied by a significant attenuation of tubulointerstitial fibrosis at 4 wk. The downregulation of eNOS protein expression in CsA-treated rat kidney was markedly upregulated by pravastatin treatment, although intrarenal renin expression was unaffected. Renal dysfunction induced by CsA significantly improved with administration of pravastatin at a dose of 20 mg/kg. Neither CsA nor pravastatin influenced serum lipid or high-sensitivity CRP levels in the treatment groups. Thus in chronic CsA nephropathy, pravastatin effectively abrogates the progression of tubulointerstitial inflammation and fibrosis. This may support the clinical use of pravastatin.

Animals↗
PubMed2003

Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.

Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl-2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose-dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.

Animals↗
PubMed2003

Bone morphogenetic protein-7 inhibits constitutive and interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in human mesangial cells: role for JNK/AP-1 pathway.

Bone morphogenetic protein-7 (BMP-7), which belongs to the TGF-beta superfamily, has been shown to reduce macrophage infiltration and tissue injury in animal models of inflammatory renal disease. To explore the mechanism involved in the anti-inflammatory effect, we investigated the effect of BMP-7 on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells. BMP- 7 significantly inhibited constitutive and IL-1 beta-induced MCP-1 protein production and MCP-1 mRNA expression by mesangial cells in a time- and concentration-dependent manner. BMP-7 also inhibited IL-1 beta-induced monocyte chemotactic activity released from the mesangial cells. We examined the role of transcription factors NF-kappa B and AP-1 in BMP-7 inhibition of IL-1 beta-induced MCP-1 expression. IL-1 beta increased NF-kappa B and AP-1 activity and both transcription factors mediated IL-1 beta-induced MCP-1 expression in mesangial cells. BMP-7 inhibited IL-1 beta-induced AP-1 activity in a concentration-dependent manner. In contrast, IL-1 beta-induced NF-kappa B activity and I kappa B alpha degradation were not affected by BMP-7. Furthermore, IL-1 beta-induced phosphorylation of c-Jun N-terminal kinase was inhibited by BMP-7. These data suggest that BMP-7 inhibits constitutive and IL-1 beta-induced MCP-1 expression in human mesangial cells partly by inhibiting c-Jun N-terminal kinase activity and subsequent AP-1 activity, and provide new insight into the therapeutic potential of BMP-7 in the inflammatory renal diseases.

Bone Morphogenetic Protein 7↗