Angiotensin II, via AT1 and AT2 Receptors and NF-κB Pathway, Regulates the Inflammatory Response in Unilateral Ureteral Obstruction

• DOI: 10.1097/01.asn.0000130564.75008.f5
• Publication Date: 2004-10-23T14:37:06Z
• Authors: Vanesa Esteban; Oscar Lorenzo; Mo[Combining Acut...; Yusuke Suzuki; Sergio Mezzano; Julia Blanco; Mathias Kretzler; Takeshi Sugaya; Jesu[Combining Ac...; Marta Ruiz-Ortega
• Keywords: Proinflammatory cytokine; Monocyte; Infiltration (HVAC)

Inflammatory cell infiltration plays a key role in the onset and progression of renal injury. The NF-κB participates inflammatory response, regulating many proinflammatory genes. Angiotensin II (Ang II), via AT1 AT2 receptors, activates NF-κB. Although contribution Ang to kidney damage is already established, receptor subtype involved recruitment not clear. For investigating this issue, unilateral ureteral obstruction (UUO) model was used mice, blocking production/receptors pathway. Two days after UUO, obstructed kidneys wild-type mice presented marked interstitial increased activity. Treatment with or antagonists partially decreased activation, whereas only blockade diminished monocyte infiltration. Obstructed AT1-knockout showed activation; both processes were abolished by an antagonist, suggesting AT2/NF-κB involvement recruitment. In angiotensin-converting enzyme inhibition combined therapy plus blocked infiltration, upregulation NF-κB–related Therefore, necessary arrest completely process. two different inhibitors, pirrolidin-dithiocarbamate parthenolide, gene overexpression. These data show that II, receptors pathway, regulation may provide rationale investigate further human diseases.