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A2A Adenosine Receptor Agonist and PDE4 Inhibition Delays Inflammation but Fails to Reduce Injury in Experimental Obstructive Nephropathy.
- Source :
- Nephron Experimental Nephrology; 2005, Vol. 100 Issue 3, pe113-e123, 11p
- Publication Year :
- 2005
-
Abstract
- Background: Renal interstitial inflammation is a consequence of unilateral ureteral obstruction (UUO). Following ischemia/reperfusion, adenosine reduces renal inflammation and injury, effects which are potentiated by type 4 phosphodiesterase inhibitors. We therefore studied the effects of A<subscript>2A</subscript> adenosine receptor agonist (ATL146e), and PDE4 inhibitor (rolipram) in mice subjected to UUO. Methods: Mice were subjected to UUO or sham operation, and received either vehicle or ATL146e + rolipram by osmotic minipump for 1 or 7 days. At 1, 3, 7, or 14 days after operation, renal macrophage infiltration, apoptosis, proliferation, tubular atrophy, and interstitial fibrosis were quantitated, and expressions of IL-6 and TGF-β mRNA were determined. Results: ATL146e + rolipram reduced macrophage infiltration by 40% after 3 days UUO (p < 0.05). Tubular apoptosis, tubular atrophy, and interstitial fibrosis were increased by 7 or 14 days UUO, but were unaffected by ATL146e + rolipram. However, cellular proliferation was increased by ATL146e + rolipram in the obstructed kidney. ATL146e + rolipram had no effect on the renal expression of IL-6 and TGF-β mRNA. Conclusions: A<subscript>2A </subscript>receptor activation and PDE4 inhibition transiently reduce renal macrophage infiltration, but do not ameliorate the renal response to UUO. We speculate that the persistent stimulus for inflammation triggered by UUO cannot be reversed by agents that suppress inflammatory cell activation alone. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Subjects :
- INFLAMMATION
ISCHEMIA
ADENOSINES
KIDNEY diseases
FIBROSIS
CELL proliferation
Subjects
Details
- Language :
- English
- ISSN :
- 16602129
- Volume :
- 100
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Nephron Experimental Nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 17312030
- Full Text :
- https://doi.org/10.1159/000085057