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Mediators of Inflammation
Volume 2009 (2009), Article ID 860565, 11 pages
Research Article

Chemokine Receptor and Ligand Upregulation in the Diaphragm during Endotoxemia and Pseudomonas Lung Infection

1Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada H2X 2P2
2UPRES EA2397 Université, Pierre et Marie Curie, 75005 Paris, France
3Respiratory Division, McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1

Received 22 July 2008; Revised 5 February 2009; Accepted 9 February 2009

Academic Editor: Dennis Daniel Taub

Copyright © 2009 Alexandre Demoule et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Sepsis-induced diaphragmatic inflammation has been associated with respiratory failure, but the role of chemokines in this process has not been evaluated. Here we sought to study the local expression and molecular regulation of the chemokines, regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP)-1 , in the murine diaphragm during sepsis. Constitutive expression levels of RANTES and MIP-1 , as well as their receptors, CCR1 and CCR5, were significantly higher in diaphragm than limb muscle. Sepsis was induced by acute lipopolysaccharide (LPS) delivery or subacutely by intratracheal administration of live Pseudomonas aeruginosa bacteria. Both sepsis models triggered a marked upregulation of RANTES and MIP-1 in the diaphragm. In vitro, stimulation of diaphragmatic muscle cells with LPS also led to RANTES upregulation. Inhibition of the NF-kB pathway using pharmacologic or dominant negative genetic approaches blocked the LPS-induced RANTES upregulation, while free radical scavengers had no effect. We conclude that sepsis leads to greatly increased expression of RANTES, MIP-1 and their cognate receptors in the diaphragm. Manipulation of the NF-kB pathway and other regulators of chemokine expression in the diaphragm could represent a novel method for mitigating the skeletal muscle inflammatory response associated with sepsis-induced diaphragmatic dysfunction.