Enhanced expression of group IIA secreted phospholipase A2 by elevated glucose levels in cytokine-stimulated rat mesangial cells and in kidneys of diabetic rats
| Autor: | K. Scholz-Pedretti, Fierlbeck W, Kaszkin M, Helmut Geiger, Vlachojannis Gj, Pfeilschifter J |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Renal glomerulus medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Kidney Sensitivity and Specificity Phospholipases A Streptozocin Proinflammatory cytokine Diabetes Mellitus Experimental Diabetic nephropathy Rats Sprague-Dawley Internal medicine Diabetes mellitus medicine Animals Diabetic Nephropathies RNA Messenger Promoter Regions Genetic Cells Cultured Probability Analysis of Variance Mesangial cell business.industry General Medicine medicine.disease Streptozotocin Blotting Northern Glomerular Mesangium Rats Disease Models Animal Phospholipases A2 medicine.anatomical_structure Cytokine Endocrinology Gene Expression Regulation Nephrology Enzyme Induction Hyperglycemia Cytokines Female business medicine.drug |
| Zdroj: | Clinical nephrology. 63(5) |
| ISSN: | 0301-0430 |
| Popis: | Background: Group IIA secreted phospholipase A 2 (SPLA 2 -IIA) has been implicated in various inflammatory processes including the kidney. Previously it has been shown that potent proinflammatory cytokines such as interleukin 1β (IL-1β) increase sPLA 2 -IIA expression and secretion in rat mesangial cells. Aim: The present study examines the effects of glucose on sPLA 2 -IIA regulation in interleukin-1β (IL-1β) treated mesangial cell cultures and in diabetic kidneys of Sprague-Dawley rats. Materials and Methods: Rat mesangial cells were grown either in low glucose (5,55 mM D-Glucose) or high glucose (25 mM) conditions followed by assessment of sPLA 2 -IIA transcription, expression and secretion after 24 h. The model of streptozotocin induced diabetes mellitus in Sprague-Dawley rats was used for the in vivo experiments. Diabetic kidneys where examined for sPLA 2 -IIA-mRNA and -protein expression as well as IL-1β-levels at 2, 4 and 6 weeks after induction of diabetes mellitus. Results: Increased concentration of glucose had a weak, but significant stimulatory effect on sPLA 2 -IIA expression, which was markedly up-regulated (2 - 3-fold) in IL-1β treated mesangial cells compared to the levels obtained in low glucose medium. Concerning the underlying mechanism, we found that high concentration of glucose increased the activity of the rat sPLA 2 -IIA-promoter, whereas mRNA stability was not affected. Furthermore, the in vivo experiments revealed a marked up-regulation of sPLA 2 -IIA mRNA and protein in the diabetic rat kidneys 2 - 4 weeks after induction. Since the strong up-regulation of sPLA 2 -IIA in vitro under high glucose conditions occurred mainly in presence of cytokine, we measured the levels of IL-1β in diabetic kidneys by ELISA. We detected rat IL-1β only in diabetic, but not in control rat kidneys. Conclusions: The changes of sPLA 2 -IIA expression under increased glucose concentrations as well as in diabetic rat kidneys suggest a function of this enzyme as an acute phase protein providing lipid autacoids that may contribute to early changes in the course of diabetic nephropathy. |
| Databáze: | OpenAIRE |
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