TY - JOUR T1 - Human recombinant lysozyme downregulates advanced glycation endproduct-induced interleukin-6 production and release in an in-vitro model of human proximal tubular epithelial cells. JF - Exp Biol Med (Maywood) Y1 - 2014 A1 - Gallo, Davide A1 - Cocchietto, Moreno A1 - Masat, Elisa A1 - Agostinis, Chiara A1 - Harei, Elisa A1 - Veronesi, Paolo A1 - Sava, Gianni KW - Cell Line KW - Cell Movement KW - Cell Survival KW - Chemokine CX3CL1 KW - Diabetic Nephropathies KW - Down-Regulation KW - Epithelial Cells KW - Glycosylation End Products, Advanced KW - Humans KW - Inflammation Mediators KW - Interleukin-18 KW - Interleukin-6 KW - Kidney Tubules, Proximal KW - Macrophage Activation KW - Macrophages KW - Muramidase KW - Recombinant Proteins KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - U937 Cells AB -

Diabetic nephropathy is the leading cause of chronic renal disease and one of the major causes of cardiovascular mortality. Evidence suggests that its progression is due to the chronic hyperglycemia consequent to the production and accumulation of advanced glycation endproducts (AGEs). Lysozyme was shown to posses AGE-sequestering properties and the capacity to reduce the severity of the early stage manifestations of the diabetic nephropathy. This study was aimed to contribute to the understanding the molecular mechanisms of lysozyme effectiveness in the diabetic nephropathy, using an in-vitro cellular model, represented by the HK-2 cells, human proximal tubular epithelial cells. Lysozyme significantly reduced the AGE-induced IL-6 mRNA and an ELISA assay showed also a decreased release of the functional protein with a dose-dependent trend. In addition, lysozyme prevented macrophage recruitment, suggesting its capacity to elicit an anti-inflammatory action. We may conclude that the protective action of lysozyme on the nephrotoxic effects of AGE may depend, at least in part, on its ability to prevent the production and release of inflammatory mediators, such as IL-6 and to reduce macrophage recruitment in the inflammatory sites.

VL - 239 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24495950?dopt=Abstract ER -