title: AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?
abstract: Advanced glycation end products (AGEs) can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293) upon exposure to 200 μg/mL bovine serum albumine (BSA) or AGEs-BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE) and heat shock proteins (HSPs) 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6), HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs-BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells.
authors: Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomical Sciences and Veterinary Medicine Bucharest, 105 Splaiul Independentei, district 5, Bucharest 050097, Romania. irensro@yahoo.com.
authors: Andreea Iren
authors: AI
authors: Serban
authors: Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomical Sciences and Veterinary Medicine Bucharest, 105 Splaiul Independentei, district 5, Bucharest 050097, Romania. lory_stanca@yahoo.com.
authors: Loredana
authors: L
authors: Stanca
authors: Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomical Sciences and Veterinary Medicine Bucharest, 105 Splaiul Independentei, district 5, Bucharest 050097, Romania. ancadinischiotu@yahoo.com.|Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, district 5, Bucharest 050095, Romania. ancadinischiotu@yahoo.com.
authors: Ovidiu Ionut
authors: OI
authors: Geicu
authors: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, district 5, Bucharest 050095, Romania. ancadinischiotu@yahoo.com.
authors: Anca
authors: A
authors: Dinischiotu
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D013482:Superoxide Dismutase; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D016207:Cytokines; D017127:Glycation End Products, Advanced; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D013482:Superoxide Dismutase
keywords: HEK 293 cells; advanced glycation end products; heat-shock proteins; inflammation; oxidative stress