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

Introduction: The nuclear factor-B (NF-B) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-B pathway linked to renal inflammation. Although both AT(1) and AT(2) receptors are involved in Ang II-mediated NF-B activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1 (IL-1) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-B. Materials and methods: In vitro studies were done in primary cultured rat mesangial cells. NF-B pathway was evaluated by phosphorylated levels of p65/IB 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-1 caused a synergistic activation of the NF-B pathway and a marked upregulation of proinflammatory factors under NF-B control, including monocyte chemoattractant protein-1. The AT(1), but not AT(2), antagonist abolished the synergistic effect on NF-B activation and proinflammatory genes caused by coincubation of Ang II and IL-1. Conclusions: These data indicates that Ang II, via AT(1)/NF-B pathway activation, cooperates with IL- to increase the inflammatory response in mesangial cells.