Chemokine Receptor and Ligand Upregulation in the Diaphragm during Endotoxemia and Pseudomonas Lung Infection
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 molecu...
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| Format: | Article |
| Language: | English |
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Wiley
2009-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2009/860565 |
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| author | Alexandre Demoule Maziar Divangahi Linda Yahiaoui Gawiyou Danialou Dusanka Gvozdic Basil J. Petrof |
| author_facet | Alexandre Demoule Maziar Divangahi Linda Yahiaoui Gawiyou Danialou Dusanka Gvozdic Basil J. Petrof |
| author_sort | Alexandre Demoule |
| collection | DOAJ |
| description | 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)-1α, in the murine diaphragm during sepsis. Constitutive
expression levels of RANTES and MIP-1α, 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-1α 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-1α 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. |
| format | Article |
| id | doaj-art-c45efecbb93c4e189f0c8c22417ea054 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c45efecbb93c4e189f0c8c22417ea0542025-08-20T02:18:48ZengWileyMediators of Inflammation0962-93511466-18612009-01-01200910.1155/2009/860565860565Chemokine Receptor and Ligand Upregulation in the Diaphragm during Endotoxemia and Pseudomonas Lung InfectionAlexandre Demoule0Maziar Divangahi1Linda Yahiaoui2Gawiyou Danialou3Dusanka Gvozdic4Basil J. Petrof5Meakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaMeakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaMeakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaMeakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaMeakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaMeakins-Christie Laboratories, McGill University, Montreal, QC, H2X 2P2, CanadaSepsis-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)-1α, in the murine diaphragm during sepsis. Constitutive expression levels of RANTES and MIP-1α, 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-1α 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-1α 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.http://dx.doi.org/10.1155/2009/860565 |
| spellingShingle | Alexandre Demoule Maziar Divangahi Linda Yahiaoui Gawiyou Danialou Dusanka Gvozdic Basil J. Petrof Chemokine Receptor and Ligand Upregulation in the Diaphragm during Endotoxemia and Pseudomonas Lung Infection Mediators of Inflammation |
| title | Chemokine Receptor and Ligand Upregulation in the Diaphragm
during Endotoxemia and Pseudomonas Lung Infection |
| title_full | Chemokine Receptor and Ligand Upregulation in the Diaphragm
during Endotoxemia and Pseudomonas Lung Infection |
| title_fullStr | Chemokine Receptor and Ligand Upregulation in the Diaphragm
during Endotoxemia and Pseudomonas Lung Infection |
| title_full_unstemmed | Chemokine Receptor and Ligand Upregulation in the Diaphragm
during Endotoxemia and Pseudomonas Lung Infection |
| title_short | Chemokine Receptor and Ligand Upregulation in the Diaphragm
during Endotoxemia and Pseudomonas Lung Infection |
| title_sort | chemokine receptor and ligand upregulation in the diaphragm during endotoxemia and pseudomonas lung infection |
| url | http://dx.doi.org/10.1155/2009/860565 |
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