title: Anti-Diabetic Agent Sodium Tungstate Induces the Secretion of Pro- and Anti-Inflammatory Cytokines by Human Kidney Cells.
abstract: Diabetic kidney disease (DKD) is the major cause of end stage renal disease. Sodium tungstate (NaW) exerts anti-diabetic and immunomodulatory activities in diabetic animal models. Here, we used primary cultures of renal proximal tubule epithelial cells derived from type-2-diabetic (D-RPTEC) and non-diabetic (N-RPTEC) subjects as in vitro models to study the effects of NaW on cytokine secretion, as these factors participate in intercellular regulation of inflammation, cell growth and death, differentiation, angiogenesis, development, and repair, all processes that are dysregulated during DKD. In basal conditions, D-RPTEC cells secreted higher levels of prototypical pro-inflammatory IL-6, IL-8, and MCP-1 than N-RPTEC cells, in agreement with their diabetic phenotype. Unexpectedly, NaW further induced IL-6, IL-8, and MCP-1 secretion in both N- and D-RPTEC, together with lower levels of IL-1 RA, IL-4, IL-10, and GM-CSF, suggesting that it may contribute to the extent of renal damage/repair during DKD. Besides, NaW induced the accumulation of IκBα, the main inhibitor protein of one major pathway involved in cytokine production, suggesting further anti-inflammatory effect in the long-term. A better understanding of the mechanisms involved in the interplay between the anti-diabetic and immunomodulatory properties of NaW will facilitate future studies about its clinical relevance. J. Cell. Physiol. 232: 355-362, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Centro de Microscopía Avanzada, CMA-Bío Bío, Universidad de Concepción, Concepción, Chile. romibert@gmail.com.|Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. romibert@gmail.com.|Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. romibert@gmail.com.
authors.forename: Romina
authors.initials: R
authors.lastname: Bertinat
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas and Facultad de Medicina, Centro Avanzado de Enfermedades Crónicas (ACCDiS), Universidad de Chile, Santiago, Chile.|Facultad de Ciencia, Universidad San Sebastián, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Westermeier
authors.affiliation: Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Silva
authors.affiliation: Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: Centro de Microscopía Avanzada, CMA-Bío Bío, Universidad de Concepción, Concepción, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
authors.affiliation: Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xuhang
authors.initials: X
authors.lastname: Li
authors.affiliation: Centro de Microscopía Avanzada, CMA-Bío Bío, Universidad de Concepción, Concepción, Chile. ayanez@uach.cl.|Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. ayanez@uach.cl.
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Yáñez
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D017973:Tungsten Compounds / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D048049:Extracellular Signal-Regulated MAP Kinases; D019764:Phosphoenolpyruvate Carboxykinase (ATP)