| First Author | Okada H | Year | 2006 |
| Journal | Am J Pathol | Volume | 169 |
| Issue | 5 | Pages | 1577-89 |
| PubMed ID | 17071582 | Mgi Jnum | J:114563 |
| Mgi Id | MGI:3689443 | Doi | 10.2353/ajpath.2006.060178 |
| Citation | Okada H, et al. (2006) A Possible Anti-Inflammatory Role of Angiotensin II Type 2 Receptor in Immune-Mediated Glomerulonephritis during Type 1 Receptor Blockade. Am J Pathol 169(5):1577-89 |
| abstractText | We previously reported that angiotensin II type 1 receptor (AT(1)R) blockade attenuates renal inflammation/fibrogenesis in immune-mediated glomerulonephritis via angiotensin II type 2 receptor (AT(2)R). In the present study, further in vivo experiments revealed that AT(2)R was expressed in tubular epithelial cells of nephritic kidneys in mice, and feedback activation of the renin-angiotensin system during AT(1)R blockade significantly reduced p-ERK, but not intranuclear nuclear factor-kappaB, levels via AT(2)R. This led to reduction in mRNA levels of the proinflammatory mediator monocyte chemoattractant protein-1 and overall interstitial inflammation and subsequent fibrogenesis. Specific blockade of ERK expression in tubular epithelium by anti-sense oligodeoxynucleotides also attenuated interstitial inflammation, mimicking the anti-inflammatory action of AT(2)R in nephritic kidneys. Alternatively, we succeeded in confirming such an AT(2)R function by demonstrating that AT(1)R blockade did not confer renoprotection in nephritic, AT(2)R gene-deficient mice. Additional in vitro experiments revealed that AT(2)R activation did not affect nuclear factor-kappaB activation by tumor necrosis factor-alpha in cultured tubular epithelial cells, although it inhibited ERK phosphorylation, which reduced monocyte chemoattractant protein-1 mRNA levels. These results suggest that feedback activation of AT(2)Rs in tubular epithelium of nephritic kidneys plays an important role in attenuating interstitial inflammation. |
