Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells

• Main Authors: Matilde Alique, Elsa Sánchez-López, Sandra Rayego-Mateos, Jesús Egido, Alberto Ortiz, Marta Ruiz-Ortega
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2015-03-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320314551564
• ISSN: 1470-3203; 1752-8976

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 AT 1 and AT 2 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 AT 1 and AT 2 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 AT 1 , but not AT 2 , 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 AT 1 /NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cells.