title: Advanced glycation end products upregulate angiogenic and pro-inflammatory cytokine production in human monocyte/macrophages.
abstract: Glucose can react non-enzymatically with amino groups of, for example, proteins, to yield derivatives termed advanced glycation end products (AGE), which contribute to many chronic progressive diseases associated with microvascular complications. The study aimed to determine the effect of AGE-modified albumin on THP-1 cells and human monocyte-derived macrophages. Bovine serum albumin (BSA) or human serum albumin (HSA), modified by glucose-derived AGE, was prepared by incubation with glucose for differing periods of time. Alternatively, BSA was incubated with sodium cyanoborohydride and glyoxylic acid to produce N(epsilon)-(carboxymethyl)lysine-modified BSA (CML-BSA). Stimulation for 24h of THP-1 cells with BSA, incubated for 6-8 weeks with glucose, induced significant VEGF release. Human monocyte-derived macrophages stimulated with extensively glycated HSA also showed significant VEGF release, as well as upregulation of IL-8 production, incubation for 6h with extensively glycated HSA increased release of TNFalpha and expression of tissue factor. Finally, addition of CML-BSA resulted in significant induction of TNFalpha and VEGF release. We demonstrate that a range of different methods of glycation of BSA and HSA, including CML-BSA, resulted in the induction of VEGF, TNFalpha, IL-8 and expression of tissue factor, according to length of stimulation and different glycation products used, suggesting that AGE-induced activation of macrophages may contribute to vascular complications by regulation of angiogenic, inflammatory and pro-coagulant processes.
authors.affiliation: Kennedy Institute of Rheumatology, Arthritis Research Campaign Building, Faculty of Medicine, Imperial College, 1, Aspenlea Road, Hammersmith, London W6 8LH, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pertyńska-Marczewska
authors.forename: Serafim
authors.initials: S
authors.lastname: Kiriakidis
authors.forename: Robin
authors.initials: R
authors.lastname: Wait
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beech
authors.forename: Marc
authors.initials: M
authors.lastname: Feldmann
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Paleolog
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000097:blood / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D012709:Serum Albumin / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016207:Cytokines; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D005947:Glucose