Published online before print March 17, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
,@
*Griffith University, Queensland, Australia; and Institute for Molecular Bioscience, CRC for Chronic Inflammatory Diseases and ARC Special Research Centre for Functional and Applied Genomics, The University of Queensland, Australia
@ To whom correspondence should be addressed. E-mail: D.Hume{at}imb.uq.edu.au.
An effective immune system requires rapid and appropriate activation of inflammatory mechanisms but equally rapid and effective resolution of the inflammatory state. A review of the canonical host response to gram-negative bacteria-the lipopolysaccharide-Toll-like receptor 4 signaling cascade-highlights the induction of repressors that act at each step of the activation process. These inflammation suppressor genes are characterized by their induction in response to pathogen, typically late in the macrophage activation program, and include an expanding class of dominant-negative proteins derived from alternate splicing of common signaling components. Despite the expanse of anti-inflammatory mechanisms available to an activated macrophage, the frailty of this system is apparent in the large numbers of genes implicated in chronic inflammatory diseases. This apparent lack of redundancy between inflammation suppressor genes is discussed with regard to evolutionary benefits in generating a heterogeneous population of immune cells and consequential robustness in defense against new and evolving pathogens.
Key Words: Toll-like receptor • lipopolysaccharide • macrophage
This article has been cited by other articles:
 |
|
 |
|
  M. Eisenblatter, J. Ehrchen, G. Varga, C. Sunderkotter, W. Heindel, J. Roth, C. Bremer, and A. Wall In Vivo Optical Imaging of Cellular Inflammatory Response in Granuloma Formation Using Fluorescence-Labeled Macrophages J. Nucl. Med., October 1, 2009; 50(10): 1676 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Hume Macrophages as APC and the Dendritic Cell Myth J. Immunol., November 1, 2008; 181(9): 5829 - 5835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Varga, J. Ehrchen, A. Tsianakas, K. Tenbrock, A. Rattenholl, S. Seeliger, M. Mack, J. Roth, and C. Sunderkoetter Glucocorticoids induce an activated, anti-inflammatory monocyte subset in mice that resembles myeloid-derived suppressor cells J. Leukoc. Biol., September 1, 2008; 84(3): 644 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Cao, C. Bao, E. Padalko, and C. J. Lowenstein Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling J. Exp. Med., June 9, 2008; 205(6): 1491 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Ripoll, K. M. Irvine, T. Ravasi, M. J. Sweet, and D. A. Hume Gpnmb Is Induced in Macrophages by IFN-{gamma} and Lipopolysaccharide and Acts as a Feedback Regulator of Proinflammatory Responses J. Immunol., May 15, 2007; 178(10): 6557 - 6566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bhattacharyya, D. E. Brown, J. A. Brewer, S. K. Vogt, and L. J. Muglia Macrophage glucocorticoid receptors regulate Toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase Blood, May 15, 2007; 109(10): 4313 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ehrchen, L. Steinmuller, K. Barczyk, K. Tenbrock, W. Nacken, M. Eisenacher, U. Nordhues, C. Sorg, C. Sunderkotter, and J. Roth Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes Blood, February 1, 2007; 109(3): 1265 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Foti, F. Granucci, M. Pelizzola, O. Beretta, and P. Ricciardi-Castagnoli Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach J. Leukoc. Biol., May 1, 2006; 79(5): 913 - 916. [Abstract] [Full Text] [PDF]
|
|
