The mechanism of glomerular infiltration of monocytes remains unknown in diabetic nephropathy. We examined the effect of a high glucose concentration on monocyte chemotactic peptide 1 (MCP-1) expression in human mesangial cells (MCs) by using enzyme-linked immunosorbent assay and reverse transcription coupled with polymerase chain reaction (PCR). More than a 50% increase in the MCP-1 protein production was observed in MCs cultured in high-glucose medium (450 mg/dl) as compared to normal glucose (100 mg/dl; 1,496 ± 75 vs. 966 ± 15 pg/ml after 24 h, 1,910 ± 93 vs. 1,250 ± 55 pg/ml after 48 h). Semiquantitative PCR showed that phorbol myristate acetate (100 nM) increased the ratio of PCR products for MCP-1 to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase on densitometric results at 24 h by 2.7-fold, which was prevented by calphostin C (200 nM) pretreatment. High glucose increased the ratio by 3-fold as compared to normal glucose at 24 h (0.72 ± 0.11 vs. 0.24 ± 0.01). This was also suppressed by calphostin C pretreatment. These findings demonstrate that high glucose can directly increase MCP-1 expression in MCs, which may contribute to monocyte infiltration in diabetic nephropathy, and this is regulated by protein kinase C.
Mass urine screening tests could detect asymptomatic GN in its early stages. Initial aggressive diagnosis and treatment for CHP and nephrotic-range groups may prove helpful as interventions that delay chronic kidney disease progression. These findings may assist in the development of diagnostic and management guidelines for relatively mild urinary abnormalities, such as IH or low-grade IP.
We have carried out a study with the aim of investigating the association between single nucleotide polymorphisms (SNPs) of the IL-1 gene cluster and childhood IgA nephropathy (IgAN). SNPs of the IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (RN) genes (IL1A, IL1B, and IL1RN, respectively) were analyzed in 182 patients with childhood IgAN and in 500 healthy controls. The IgAN patients were also dichotomized and compared with respect to proteinuria (<4 mg and >or=4 mg/m(2) per hour, respectively), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers, such as interstitial fibrosis, tubular atrophy, or global sclerosis. Significant differences in SNP frequencies were observed for the IL1B and IL1RN genes (rs1143627, rs3917356, and rs1143633 in the IL1B gene, and rs928940, rs439154, and rs315951 in the IL1RN gene). Moreover, rs1143627, rs3917356, and rs1143633 of IL1B were found to be significantly associated with the presence of podocyte foot process effacement. Our results suggest that the IL1B and IL1RN genes are associated with increased susceptibility to IgAN in children. They also suggest that the development of proteinuria in IgAN is related to IL1A and that podocyte foot process effacement is associated with IL1B.
Background/Aim: Cytokines play an important role in the pathogenesis of kidney diseases. The aim of the study was to investigate the impact of interleukin (IL)-1 cluster genes on diabetic nephropathy in Korean patients with type 2 diabetes mellitus (DM). Methods: We investigated –511 C/T polymorphism of IL-1β and tandem repeat polymorphism in intron 2 of IL-1 receptor antagonist in type 2 DM patients with end-stage kidney failure as compared with patients without nephropathy. Results: The IL1B2 allele was found more frequently in patients with kidney failure than in controls (57.4 vs. 46.1%, p < 0.05). An excessive homozygous carriage of IL1B2 was found in patients with kidney failure when compared with controls (30.5 vs. 18.3%, p < 0.05). The allelic frequency of IL1RN*2 was also higher in cases than in controls without nephropathy (8.4 vs. 2.8 %, p < 0.05). The carriage rate of IL1RN*2 was significantly associated with an increased risk of kidney failure (15.8 vs. 5.6%; OR 3.19, 95% CI 1.24–8.17). The risk of kidney failure was highest in those carrying both IL1RN*2 and IL1B2 (OR 3.90, 95% CI 1.34–11.40). Conclusion: IL1B2 and IL1RN*2 genotypes of the IL-1 cluster genes are associated with diabetic nephropathy in Korean patients with type 2 DM.
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