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B Activation and Monocyte Chemoattractant Protein-1 Synthesis1
Renal Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain
Angiotensin-converting enzyme (ACE) inhibitors reduce macrophage
infiltration in several models of renal injury. We approached the
hypothesis that angiotensin II (AngII) could be involved in
inflammatory cell recruitment during renal damage through the synthesis
of monocyte chemoattractant protein-1 (MCP-1). In a model of immune
complex nephritis, we observed an up-regulation of renal MCP-1 (mRNA
and protein) coincidentally with mononuclear cell infiltration that
were markedly reduced by treatment with the ACE inhibitor quinapril.
Exposure of cultured rat mesangial cells to AngII increased MCP-1 mRNA
expression (2.7-fold) and synthesis (3-fold), similar to that observed
with TNF-
. Since NF-
B is involved in the regulation of MCP-1
gene, we explored whether the effects of AngII were mediated through
NF-B activation. Untreated nephritic rats showed increased renal
NF-B activity (3.5-fold) that decreased in response to ACE
inhibition. In mesangial cells, AngII activated NF-B (4.3-fold), and
the NF-B inhibitor pyrrolidine dithiocarbamate abolished the
AngII-induced NF-B activation and MCP-1 gene expression. Our results
suggest that AngII could participate in the recruitment of mononuclear
cells through NF-B activation and MCP-1 expression by renal cells.
This could be a novel mechanism that might further explain the
beneficial effects of ACE inhibitors in progressive renal diseases.
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T. M. Behr, X. Wang, N. Aiyar, R. W. Coatney, X. Li, P. Koster, C. E. Angermann, E. Ohlstein, G. Z. Feuerstein, and J. Winaver Monocyte Chemoattractant Protein-1 is Upregulated in Rats With Volume-Overload Congestive Heart Failure Circulation, September 12, 2000; 102(11): 1315 - 1322. [Abstract] [Full Text] [PDF]
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D. N. Muller, E. M. A. Mervaala, F. Schmidt, J.-K. Park, R. Dechend, E. Genersch, V. Breu, B.-M. Loffler, D. Ganten, W. Schneider, et al. Effect of Bosentan on NF-{kappa}B, Inflammation, and Tissue Factor in Angiotensin II-Induced End-Organ Damage Hypertension, August 1, 2000; 36(2): 282 - 290. [Abstract] [Full Text] [PDF]
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 M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, S. Konig, B. Wittig, and J. Egido Angiotensin II Activates Nuclear Transcription Factor {kappa}B Through AT1 and AT2 in Vascular Smooth Muscle Cells : Molecular Mechanisms Circ. Res., June 23, 2000; 86(12): 1266 - 1272. [Abstract] [Full Text] [PDF]
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, and J. Egido ACE inhibitors and AT1 receptor antagonists--beyond the haemodynamic effect Nephrol. Dial. Transplant., May 1, 2000; 15(5): 561 - 565. [Full Text] [PDF]
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 S. Kim and H. Iwao Molecular and Cellular Mechanisms of Angiotensin II-Mediated Cardiovascular and Renal Diseases Pharmacol. Rev., March 1, 2000; 52(1): 11 - 34. [Abstract] [Full Text] [PDF]
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C. Gomez-Guerrero, N. Duque, M. T. Casado, C. Pastor, J. Blanco, F. Mampaso, F. Vivanco, and J. Egido Administration of IgG Fc Fragments Prevents Glomerular Injury in Experimental Immune Complex Nephritis J. Immunol., February 15, 2000; 164(4): 2092 - 2101. [Abstract] [Full Text] [PDF]
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S. SEGERER, P. J. NELSON, and D. SCHLÖNDORFF Chemokines, Chemokine Receptors, and Renal Disease: From Basic ScienceTo Pathophysiologic and Therapeutic Studies J. Am. Soc. Nephrol., January 1, 2000; 11(1): 152 - 176. [Abstract] [Full Text]
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D. N. Muller, R. Dechend, E. M. A. Mervaala, J.-K. Park, F. Schmidt, A. Fiebeler, J. Theuer, V. Breu, D. Ganten, H. Haller, et al. NF-{kappa}B Inhibition Ameliorates Angiotensin II-Induced Inflammatory Damage in Rats Hypertension, January 1, 2000; 35(1): 193 - 201. [Abstract] [Full Text] [PDF]
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C. E. Donovan, D. A. Mark, H. Z. He, H.-C. Liou, L. Kobzik, Y. Wang, G. T. De Sanctis, D. L. Perkins, and P. W. Finn NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation J. Immunol., December 15, 1999; 163(12): 6827 - 6833. [Abstract] [Full Text] [PDF]
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Y. WANG, G. K. RANGAN, Y.-C. TAY, Y. WANG, and D. C. H. HARRIS Induction of Monocyte Chemoattractant Protein-1 by Albumin Is Mediated by Nuclear Factor {kappa}B in Proximal Tubule Cells J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1204 - 1213. [Abstract] [Full Text]
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R. Largo, D. Gomez-Garre, K. Soto, B. Marron, J. Blanco, R. M. Gazapo, J. J. Plaza, and J. Egido Angiotensin-Converting Enzyme Is Upregulated in the Proximal Tubules of Rats With Intense Proteinuria Hypertension, February 1, 1999; 33(2): 732 - 739. [Abstract] [Full Text] [PDF]
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D. Kalra, N. Sivasubramanian, and D. L. Mann Angiotensin II Induces Tumor Necrosis Factor Biosynthesis in the Adult Mammalian Heart Through a Protein Kinase C-Dependent Pathway Circulation, May 7, 2002; 105(18): 2198 - 2205. [Abstract] [Full Text] [PDF]
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