Matilde Alique1, Elsa Sánchez-López1, Sandra Rayego-Mateos1, Jesús Egido2, Alberto Ortiz3, Marta Ruiz-Ortega4. 1. Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz Universidad Autónoma Madrid, Spain. 2. Renal Research Laboratory, IIS-Fundación Jiménez Díaz Universidad Autónoma Madrid, Spain. 3. Dialysis Unit, IIS-Fundación Jiménez Díaz Universidad Autónoma Madrid, Spain. 4. Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz Universidad Autónoma Madrid, Spain mruizo@fjd.es.
Abstract
INTRODUCTION: The nuclear factor-κB (NF-κB) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-κB pathway linked to renal inflammation. Although both AT1 and AT2 receptors are involved in Ang II-mediated NF-κB activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1β (IL-1β) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-κB. MATERIALS AND METHODS: In vitro studies were done in primary cultured rat mesangial cells. NF-κB pathway was evaluated by phosphorylated levels of p65/IκB and DNA binding activity. The Ang II receptor subtype was determined by pretreatment with AT1 and AT2 antagonists. RESULTS: In mesangial cells the simultaneous presence of Ang II and IL-1β caused a synergistic activation of the NF-κB pathway and a marked upregulation of proinflammatory factors under NF-κB control, including monocyte chemoattractant protein-1. The AT1, but not AT2, antagonist abolished the synergistic effect on NF-κB activation and proinflammatory genes caused by coincubation of Ang II and IL-1β. CONCLUSIONS: These data indicates that Ang II, via AT1/NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cells.
INTRODUCTION: The nuclear factor-κB (NF-κB) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-κB pathway linked to renal inflammation. Although both AT1 and AT2 receptors are involved in Ang II-mediated NF-κB activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1β (IL-1β) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-κB. MATERIALS AND METHODS: In vitro studies were done in primary cultured rat mesangial cells. NF-κB pathway was evaluated by phosphorylated levels of p65/IκB and DNA binding activity. The Ang II receptor subtype was determined by pretreatment with AT1 and AT2 antagonists. RESULTS: In mesangial cells the simultaneous presence of Ang II and IL-1β caused a synergistic activation of the NF-κB pathway and a marked upregulation of proinflammatory factors under NF-κB control, including monocyte chemoattractant protein-1. The AT1, but not AT2, antagonist abolished the synergistic effect on NF-κB activation and proinflammatory genes caused by coincubation of Ang II and IL-1β. CONCLUSIONS: These data indicates that Ang II, via AT1/NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cells.
Authors: Claudia M Lucero; Lucas Marambio-Ruiz; Javiera Balmazabal; Juan Prieto-Villalobos; Marcelo León; Paola Fernández; Juan A Orellana; Victoria Velarde; Juan C Sáez; Gonzalo I Gómez Journal: Int J Mol Sci Date: 2022-09-03 Impact factor: 6.208