~ 44 ~ The Pharma Innovation Journal 2015; 3(12): 44-48 ISSN: 2277- 7695 TPI 2015; 3(12): 44-48 © 2015 TPI www.thepharmajournal.com Received: 09-01-2015 Accepted: 12-02-2015 Galván-Moroyoqui JM Departamento de Medicina y Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Candia-Plata MC Departamento de Medicina y Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Martínez-Soto JM Programa de Doctorado en Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Soto-Guzmán JA Departamento de Medicina y Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Bolado Martínez E Departamento de Ciencias Químico-Biológicas Universidad de Sonora, Hermosillo, Sonora, Mexico. Camacho-Villa AY Departamento de Medicina, Universidad Durango Santander. Campus Hermosillo, Sonora, Mexico. López-Soto LF Departamento de Medicina y Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Correspondence: López-Soto LF Departamento de Medicina y Ciencias de la Salud Universidad de Sonora, Hermosillo, Sonora, Mexico. Glycated ferritin induces activation and expression of tlr2 and tlr4 in human peripheral blood macrophages Galván-Moroyoqui JM, Candia-Plata MC, Martínez-Soto JM, Soto-Guzmán JA, Bolado Martínez E, Camacho-Villa AY, López-Soto LF Abstract Recently it has been proposed that serum ferritin might play a role in the pathogenesis of metabolic diseases, however so far unknown mechanism by which ferritin involved in these disorders. It has been reported that ferritin can be modified by glycation and peroxidation, through a process that occurs naturally but is increased in subjects with diabetes, called non-enzymatic glycation. This work was carried out modifying ferritin using an in vitro model of glycation process and used these modified protein by glycation as a stimulus in peripheral blood mononuclear cells (PBMN). We observed that ferritin glycated activates the expression of TLR2 and TLR4 in cells CD14+ derived from PBMN cells and further these PBMN cells increase the secretion of pro-inflammatory cytokines IL-6 and IL-8. Our results suggest that the activation of the TLR signaling pathway, is stimulated with glycated ferritin, increasing the production of pro-inflammatory cytokines in the supernatants of the PBMC, these data strongly suggesting that this modified protein acts as a potent inflammatory stimulus activating the CD14+ cells, it acting in a similar way as is done by advanced glycation endproducts, by activating TLRs and induction of cytokine secretion, which suggests that it could play a key role in the onset of chronic inflammation observed in patients with diabetes and which could contribute to the development of vascular complications in these patients. Keywords: TLRs, glycation, ferritin, inflammation, macrophages. 1. Introduction Diabetes mellitus type 2 (DM2) is a heterogeneous group of complex metabolic condition characterized by increased blood glucose that affects the action and/or insulin secretion, which cause dysfunction of multiple organs or tissues [1] . Complications of type 2 diabetes are often associated with macro and microvascular complications, mostly due to the accelerated atherogenesis, oxidative stress and the inflammatory state of these patients [1] . In DM2, the glycation of proteins and lipids produced by continuous hyperglycemic state, contributing to the formation of advanced glycation end products (AGEs), which are especially accumulate at sites of atherosclerotic lesions binding to RAGE receptors (receptor for AGEs) in endothelial cells, which interaction activates intracellular signaling pathways that mediate a pro- inflammatory effect on them through the activation of toll-like receptors [2, 3] . A modification by glycation of various proteins in DM2 patients is considered as inductors in the development of atherosclerosis and has been considered one of the main therapeutic targets [4-6] . Recently it has been reported in patients with DM2 elevated serum ferritin, which has suggested that alterations in the metabolism of iron could be part of the metabolic syndrome of DM2, which is associated with insulin resistance, hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension and central obesity [7] . It has also been reported that hyper-ferritin correlates with the onset of vascular complications in patients with type 2 diabetes, such as diabetic retinopathy, diabetic nephropathy and vascular dysfunction [8-10] , however, these reports only show a qualitative correlation between serum ferritin with complications of DM2 and classical markers of disease, such as hyperinsulinemia and hyperglycemia, whereas the biochemical mechanisms by which serum ferritin may contribute to T2DM have not been explored. Ferritin is the protein responsible for intracellular iron storage and detoxification [11-15] . Ferritin molecule is a heteropolymer of 24 subunits of two different types: L and H, with a molecular weight of 20 kDa each, formed by four helical chains. Variations in the content of subunits that make up the molecule determine the existence of different isoferritins, which are divided