Effects of different LDL particles on inflammatory molecules in human mesangial cells
| Autor: | Eleonora Santini, Anna Solini, Roberto Lupi, Simona Baldi, Stephanie Madec, D. Chimenti, Eleuterio Ferrannini |
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| Rok vydání: | 2008 |
| Předmět: |
Glycation End Products
Advanced Programmed cell death medicine.medical_specialty Renal glomerulus Endocrinology Diabetes and Metabolism Apoptosis Inflammation Proinflammatory cytokine Glomerulosclerosis Human mesangial cells Apoptosis Glomerulosclerosis Human mesangial cells Inflammation LDL particles Antigens CD Internal medicine Internal Medicine medicine Humans RNA Messenger CD40 Antigens LDL particles biology Mesangial cell Interleukin-6 business.industry Kinase Molecular biology Glomerular Mesangium Lipoproteins LDL Fibronectin Endocrinology biology.protein lipids (amino acids peptides and proteins) Macrophage migration inhibitory factor medicine.symptom business |
| Zdroj: | Diabetologia. 51:2117-2125 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-008-1127-4 |
| Popis: | Inflammation is a mechanism of glomerular damage in chronic glomerulopathies. LDL may increase the production of inflammatory cytokines in renal tissues. However, the relative role of native, oxidised and glycated LDL in promoting this process has been only partially elucidated. We tested the inflammatory and proapoptotic effects of native, oxidised and glycated LDL in human mesangial cells (HMCs) by measuring levels of IL6, CD40 and macrophage migration inhibitory factor (MIF) genes, MIF protein, release of IL6, soluble CD40, fibronectin and laminin, early and late apoptosis, and extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation. IL6 and CD40 mRNA were dose-dependently upregulated by all three species; this was closely paralleled by their increased release. MIF mRNA was potently stimulated by modified LDL, as confirmed by immunostaining. Fibronectin and laminin release was stimulated by both oxidised and glycated, but not native, LDL. All LDL species induced some increase in late, but not early, apoptosis, and similarly activated JNK2/3 phosphorylation; in contrast, ERK1/2 phosphorylation was more strongly upregulated by oxidised than either native or glycated LDL. In HMCs, the production and release of IL6 and CD40 is stimulated by both native and modified LDL, while MIF is more strongly stimulated by oxidised LDL. Regarding the pattern of mesangial expansion, fibronectin and laminin are upregulated by oxidised and glycated LDL. Apoptosis, if modest, is induced by all species. Intracellular signalling of native and modified LDL involves JNK2/3 and, perhaps more specifically, ERK1/2. Tight control of the lipid profile may be useful in preserving kidney function in patients with metabolic alterations. |
| Databáze: | OpenAIRE |
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