Molecular Biology of the Cell click for ASCB 2009 Annual Meeting page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E02-08-0498 on November 18, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E02-08-0498v1
14/2/764    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vega, V. L.
Right arrow Articles by De Maio, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vega, V. L.
Right arrow Articles by De Maio, A.

Vol. 14, Issue 2, 764-773, February 2003

Geldanamycin Treatment Ameliorates the Response to LPS in Murine Macrophages by Decreasing CD14 Surface Expression

Virginia L. Vega, and Antonio De Maio*

Division of Pediatric Surgery and Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Geldanamycin (GA) is an antibiotic produced by Actinomyces, which specifically inhibits the function of the heat shock protein 90 family. Treatment of a murine macrophage cell line (J774) with GA resulted in a reduced response to Escherichia coli lipopolysaccharide (LPS) as visualized by a decrease of NF-kappa B translocation into the nucleus and secretion of tumor necrosis factor alpha  (TNF-alpha ). To elucidate the mechanism of this effect, the expression of CD14, the formal LPS receptor, was analyzed. Cells treated with GA showed a reduced level of surface CD14 detected by immunostaining, whereas the expression of other surface receptors, such as FC-gamma receptor and tumor necrosis factor receptors (TNF-R1 and TNF-R2), was unaffected. The reduced surface level of CD14 was not due to a reduction in its expression because CD14 steady state mRNA levels or the total cellular pool of CD14 was not altered by GA treatment. Surface CD14 was more rapidly internalized after GA treatment (2-3 h) than after incubation with cycloheximide. Immunostaining of permeabilized cells after GA treatment revealed a higher intracellular content of CD14 colocalizing with calnexin, an endoplasmic reticulum (ER) protein. These results suggest that the decrease in CD14 surface expression after GA treatment is due to rapid internalization without new replacement. These effects may be due to the inhibition of Hsp90 and Grp94 by GA in macrophages.

* Corresponding author. E-mail address: ademaio{at}jhmi.edu.

Molecular Biology of the Cell
Vol. 14, 764-773, February 2003
Copyright © 2003 by The American Society for Cell Biology


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
P. Mandrekar, D. Catalano, V. Jeliazkova, and K. Kodys
Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-{alpha} regulation
J. Leukoc. Biol., November 1, 2008; 84(5): 1335 - 1345.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
V. Poulaki, E. Iliaki, N. Mitsiades, C. S. Mitsiades, Y. N. Paulus, D. V. Bula, E. S. Gragoudas, and J. W. Miller
Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis
FASEB J, July 1, 2007; 21(9): 2113 - 2123.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H.-Y. Hsu, H.-L. Wu, S.-K. Tan, V. P.-H. Li, W.-T. Wang, J. Hsu, and C.-H. Cheng
Geldanamycin Interferes with the 90-kDa Heat Shock Protein, Affecting Lipopolysaccharide-Mediated Interleukin-1 Expression and Apoptosis within Macrophages
Mol. Pharmacol., January 1, 2007; 71(1): 344 - 356.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. Y. Chen and W. E. Balch
The Hsp90 Chaperone Complex Regulates GDI-dependent Rab Recycling
Mol. Biol. Cell, August 1, 2006; 17(8): 3494 - 3507.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. L. Vega and A. De Maio
Increase in Phagocytosis after Geldanamycin Treatment or Heat Shock: Role of Heat Shock Proteins
J. Immunol., October 15, 2005; 175(8): 5280 - 5287.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. De Nardo, P. Masendycz, S. Ho, M. Cross, A. J. Fleetwood, E. C. Reynolds, J. A. Hamilton, and G. M. Scholz
A Central Role for the Hsp90{middle dot}Cdc37 Molecular Chaperone Module in Interleukin-1 Receptor-associated-kinase-dependent Signaling by Toll-like Receptors
J. Biol. Chem., March 18, 2005; 280(11): 9813 - 9822.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Panopoulos, M. Harraz, J. F. Engelhardt, and E. Zandi
Iron-mediated H2O2 Production as a Mechanism for Cell Type-specific Inhibition of Tumor Necrosis Factor {alpha}-Induced but Not Interleukin-1{beta}-induced I{kappa}B Kinase Complex/Nuclear Factor-{kappa}B Activation
J. Biol. Chem., January 28, 2005; 280(4): 2912 - 2923.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J.-F. Pittet, H. Lee, M. Pespeni, A. O'Mahony, J. Roux, and W. J. Welch
Stress-Induced Inhibition of the NF-{kappa}B Signaling Pathway Results from the Insolubilization of the I{kappa}B Kinase Complex following Its Dissociation from Heat Shock Protein 90
J. Immunol., January 1, 2005; 174(1): 384 - 394.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. F. Yang, R. T. Poon, Y. Luo, C. K. Cheung, D. W. Ho, C. M. Lo, and S. T. Fan
Up-Regulation of Vascular Endothelial Growth Factor (VEGF) in Small-for-Size Liver Grafts Enhances Macrophage Activities through VEGF Receptor 2-Dependent Pathway
J. Immunol., August 15, 2004; 173(4): 2507 - 2515.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. L. Soldano, A. Jivan, C. V. Nicchitta, and D. T. Gewirth
Structure of the N-terminal Domain of GRP94: BASIS FOR LIGAND SPECIFICITY AND REGULATION
J. Biol. Chem., November 28, 2003; 278(48): 48330 - 48338.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]