Effects of high glucose on cytokine-induced nerve growth factor (NGF) expression in rat renal mesangial cells
Autor: | Uwe Otten, Karl-Friedrich Beck, Helmut Geiger, Heiko Mühl, Andrea Huwiler, Josef Pfeilschifter, Katharina Plüss, Klaus Heese, Meik Helmut Behrens, Wolfgang Fierlbeck |
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Rok vydání: | 2002 |
Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Glomerular Mesangial Cell Gene Expression Inflammation Biology Biochemistry Rats Sprague-Dawley Internal medicine Nerve Growth Factor medicine Animals Diabetic Nephropathies RNA Messenger Protein kinase C Pharmacology Mesangial cell Tumor Necrosis Factor-alpha Glomerular Mesangium Rats Cytokine Endocrinology Nerve growth factor Glucose biology.protein Cytokines medicine.symptom Neurotrophin Transforming growth factor Interleukin-1 |
Zdroj: | Biochemical pharmacology. 65(2) |
ISSN: | 0006-2952 |
Popis: | Nerve growth factor (NGF) accumulates at sites of inflammation and modulates local immune reactions. To characterize the mechanisms of cytokine-induced NGF expression under physiogical and pathophysiological conditions, we have used cultured glomerular mesangial cells, which play a key role in glomerular inflammatory diseases such as diabetic nephropathy. To study the effects of high glucose on cytokine-induced NGF expression, rat mesangial cells were treated with the cytokines interleukin-1β and tumor necrosis factor α under normal (1.0 g/L) and high (4.5 g/L) glucose concentrations. In the presence of high glucose concentrations, the cytokines drastically potentiated NGF protein but not mRNA expression when compared to physiological glucose levels. The specific protein kinase C inhibitors Ro31-8220 and CGP41251 suppressed cytokine-induced NGF expression. Moreover, blocking the oxidative activation of the protein kinase C pathway by N -acetylcysteine inhibited glucose effects on NGF synthesis. Neutralizing antibodies against transforming growth factor-β inhibited cytokine-induced NGF expression under normal glucose concentrations but not under high glucose conditions. Enhanced expression of NGF under high glucose conditions may contribute to kidney diseases such as diabetic nephropathy. |
Databáze: | OpenAIRE |
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