| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
B Inhibitors as Potential Novel Anti-Inflammatory Agents for the Treatment of Immune Glomerulonephritis
From the Renal and Vascular Research Laboratory,* Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain; the Hospital Clínico San Carlos, Madrid, Spain; and the Kidney Disease Section, National Institutes of Health, Bethesda, Maryland
Nuclear factor (NF)-
B regulates several genes implicated in the inflammatory response and represents an interesting therapeutic target. We examined the effects of gliotoxin (a fungal metabolite) and parthenolide (a plant extract), which possess anti-inflammatory activities in vitro, on the progression of experimental glomerulonephritis. In the anti-Thy 1.1 rat model, gliotoxin (75 µg/rat/day, 10 days, n = 18 rats) markedly reduced proteinuria, glomerular lesions, and monocyte infiltration. In anti-mesangial cell nephritis in mice, parthenolide (70 µg/mouse/day, 7 days, n = 17 mice) significantly decreased proteinuria, hematuria, and glomerular proliferation. NF-B activity, localized in glomerular and tubular cells, was attenuated by either gliotoxin or parthenolide, in association with diminished renal expression of monocyte chemoattractant protein-1 and inducible nitric oxide synthase. In cultured mesangial cells and monocytes, gliotoxin and parthenolide inhibited NF-B activation and expression of inflammatory genes induced by lipopolysaccharide and cytokines, by blocking the phosphorylation/degradation of the IB
subunit. In summary, gliotoxin and parthenolide prevent proteinuria and renal lesions by inhibiting NF-B activation and expression of regulated genes. This may represent a novel approach for the treatment of immune and inflammatory renal diseases.
This article has been cited by other articles:
 |
|
 |
|
  B. Munoz-Garcia, J. A. Moreno, O. Lopez-Franco, A. B. Sanz, J. L. Martin-Ventura, J. Blanco, A. Jakubowski, L. C. Burkly, A. Ortiz, J. Egido, et al. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Enhances Vascular and Renal Damage Induced by Hyperlipidemic Diet in ApoE-Knockout Mice Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2061 - 2068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Panzer, O. M. Steinmetz, J.-E. Turner, C. Meyer-Schwesinger, C. von Ruffer, T. N. Meyer, G. Zahner, C. Gomez-Guerrero, R. M. Schmid, U. Helmchen, et al. Resolution of renal inflammation: a new role for NF-{kappa}B1 (p50) in inflammatory kidney diseases Am J Physiol Renal Physiol, August 1, 2009; 297(2): F429 - F439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sanchez-Lopez, S. Rayego, R. Rodrigues-Diez, J. S. Rodriguez, R. Rodrigues-Diez, J. Rodriguez-Vita, G. Carvajal, L. S. Aroeira, R. Selgas, S. A. Mezzano, et al. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-{kappa}B J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1513 - 1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Diaz Encarnacion, G. M. Warner, C. E. Gray, J. Cheng, H. K. H. Keryakos, K. A. Nath, and J. P. Grande Signaling pathways modulated by fish oil in salt-sensitive hypertension Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1323 - F1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Sanz, P. Justo, M. D. Sanchez-Nino, L. M. Blanco-Colio, J. A. Winkles, M. Kreztler, A. Jakubowski, J. Blanco, J. Egido, M. Ruiz-Ortega, et al. The Cytokine TWEAK Modulates Renal Tubulointerstitial Inflammation J. Am. Soc. Nephrol., April 1, 2008; 19(4): 695 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hidaka, Y. Suzuki, M. Yamashita, T. Shibata, Y. Tanaka, S. Horikoshi, and Y. Tomino Amelioration of Crescentic Glomerulonephritis by RhoA Kinase Inhibitor, Fasudil, through Podocyte Protection and Prevention of Leukocyte Migration Am. J. Pathol., March 1, 2008; 172(3): 603 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, L. Soltero, P. Zhang, X. R. Huang, H. Y. Lan, and H. J. Adrogue Renal inflammation is modulated by potassium in chronic kidney disease: possible role of Smad7 Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1123 - F1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Forslund, A. Sikio, and J. Anttinen IgA nephropathy in a patient with IgG lambda light-chain plasmacytoma: a rare coincidence Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2705 - 2708. [Full Text] [PDF]
|
|
|
|
|
|
Y. Ozawa and H. Kobori Crucial role of Rho-nuclear factor-{kappa}B axis in angiotensin II-induced renal injury Am J Physiol Renal Physiol, July 1, 2007; 293(1): F100 - F109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saadane, S. Masters, J. DiDonato, J. Li, and M. Berger Parthenolide Inhibits I{kappa}B Kinase, NF-{kappa}B Activation, and Inflammatory Response in Cystic Fibrosis Cells and Mice Am. J. Respir. Cell Mol. Biol., June 1, 2007; 36(6): 728 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lopez-Franco, P. Hernandez-Vargas, G. Ortiz-Munoz, G. Sanjuan, Y. Suzuki, L. Ortega, J. Blanco, J. Egido, and C. Gomez-Guerrero Parthenolide Modulates the NF-{kappa}B-Mediated Inflammatory Responses in Experimental Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1864 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Liu and A. B. Malik NF-{kappa}B activation as a pathological mechanism of septic shock and inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L622 - L645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sugaru, T. Nakagawa, M. Ono-Kishino, J. Nagamine, T. Tokunaga, M. Kitoh, W. E. Hume, R. Nagata, and M. Taiji SMP-534 ameliorates progression of glomerular fibrosis and urinary albumin in diabetic db/db mice Am J Physiol Renal Physiol, April 1, 2006; 290(4): F813 - F820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. I. Jalal and B. C. Kone Src Activation of NF-{kappa}B Augments IL-1{beta}-Induced Nitric Oxide Production in Mesangial Cells J. Am. Soc. Nephrol., January 1, 2006; 17(1): 99 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamada, S. Katsuma, T. Adachi, A. Hirasawa, S. Shiojima, T. Kadowaki, Y. Okuno, T.-a. Koshimizu, S. Fujii, Y. Sekiya, et al. Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis PNAS, May 24, 2005; 102(21): 7736 - 7741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pullerits, M. Bokarewa, I.-M. Jonsson, M. Verdrengh, and A. Tarkowski Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis Rheumatology, January 1, 2005; 44(1): 32 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Esteban, O. Lorenzo, M. Ruperez, Y. Suzuki, S. Mezzano, J. Blanco, M. Kretzler, T. Sugaya, J. Egido, and M. Ruiz-Ortega Angiotensin II, via AT1 and AT2 Receptors and NF-{kappa}B Pathway, Regulates the Inflammatory Response in Unilateral Ureteral Obstruction J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1514 - 1529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Heckmann, C. Waltzinger, P. Jolicoeur, M. Dreano, M. H. Kosco-Vilbois, and Y. Sagot IKK2 Inhibitor Alleviates Kidney and Wasting Diseases in a Murine Model of Human AIDS Am. J. Pathol., April 1, 2004; 164(4): 1253 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Martin-Ventura, L. M. Blanco-Colio, B. Munoz-Garcia, A. Gomez-Hernandez, A. Arribas, L. Ortega, J. Tunon, and J. Egido NF-{kappa}B Activation and Fas Ligand Overexpression in Blood and Plaques of Patients With Carotid Atherosclerosis: Potential Implication in Plaque Instability Stroke, February 1, 2004; 35(2): 458 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pocock, C. Gomez-Guerrero, S. Harendza, M. Ayoub, P. Hernandez-Vargas, G. Zahner, R. A. K. Stahl, and F. Thaiss Differential Activation of NF-{kappa}B, AP-1, and C/EBP in Endotoxin-Tolerant Rats: Mechanisms for In Vivo Regulation of Glomerular RANTES/CCL5 Expression J. Immunol., June 15, 2003; 170(12): 6280 - 6291. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
