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CUTTING EDGE |
B1
*
Department of Biological Sciences, Wayne State University, Detroit, MI 48202; and
Department of Immunology, Saga Medical School, Saga, Japan
CD14, a GPI-linked protein, plays a pivotal role in LPS-mediated
signaling by potentiating leukocyte adherence, activation, and cytokine
production. Recent studies have identified the Toll-like receptor 4
(TLR4) as a membrane cofactor in LPS-mediated transmembrane signaling
in cytokine induction, although the mechanism responsible for this
cooperation is unknown. Using fluorescence resonance energy transfer
(RET) techniques, we demonstrate that LPS triggers a physical
association between CD14 and TLR4. Because LPS stimulation up-regulates
CD14 and TLR4 expression, it was necessary to control for the
possibility that these newly expressed molecules were associated with
one another independent of LPS stimulation. Although the calcium
ionophore A23187 increased the expression of CD14 and TLR4, they did
not exhibit energy transfer. However, following A23187 treatment, LPS
promoted physical proximity between CD14 and TLR4. Therefore, we
suggest that a close interaction between CD14 and TLR4 participates in
LPS signaling, leading to nuclear translocation of
NF-
B.
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M. T. Abreu, E. T. Arnold, L. S. Thomas, R. Gonsky, Y. Zhou, B. Hu, and M. Arditi TLR4 and MD-2 Expression Is Regulated by Immune-mediated Signals in Human Intestinal Epithelial Cells J. Biol. Chem., May 31, 2002; 277(23): 20431 - 20437. [Abstract] [Full Text] [PDF]
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J. Fan, A. Kapus, P. A. Marsden, Y. H. Li, G. Oreopoulos, J. C. Marshall, S. Frantz, R. A. Kelly, R. Medzhitov, and O. D. Rotstein Regulation of Toll-Like Receptor 4 Expression in the Lung Following Hemorrhagic Shock and Lipopolysaccharide J. Immunol., May 15, 2002; 168(10): 5252 - 5259. [Abstract] [Full Text] [PDF]
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A. E. Medvedev, P. Henneke, A. Schromm, E. Lien, R. Ingalls, M. J. Fenton, D. T. Golenbock, and S. N. Vogel Induction of Tolerance to Lipopolysaccharide and Mycobacterial Components in Chinese Hamster Ovary/CD14 Cells Is Not Affected by Overexpression of Toll-Like Receptors 2 or 4 J. Immunol., August 15, 2001; 167(4): 2257 - 2267. [Abstract] [Full Text] [PDF]
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B. W. Jones, T. K. Means, K. A. Heldwein, M. A. Keen, P. J. Hill, J. T. Belisle, and M. J. Fenton Different Toll-like receptor agonists induce distinct macrophage responses J. Leukoc. Biol., June 1, 2001; 69(6): 1036 - 1044. [Abstract] [Full Text] [PDF]
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D. Filipp, K. Alizadeh-Khiavi, C. Richardson, A. Palma, N. Paredes, O. Takeuchi, S. Akira, and M. Julius Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation PNAS, January 16, 2001; 98(2): 603 - 608. [Abstract] [Full Text] [PDF]
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