Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism
In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate sy...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/586895 |
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| author | E. K. Patterson L. J. Yao N. Ramic J. F. Lewis G. Cepinskas L. McCaig R. A. W. Veldhuizen C. M. Yamashita |
| author_facet | E. K. Patterson L. J. Yao N. Ramic J. F. Lewis G. Cepinskas L. McCaig R. A. W. Veldhuizen C. M. Yamashita |
| author_sort | E. K. Patterson |
| collection | DOAJ |
| description | In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hypothesized that lung-derived mediators generated by mechanical ventilation (MV) are amplified by peripheral organs in a “feed forward” mechanism of systemic inflammation. Herein, lung-derived mediators were collected from 129X1/SVJ mice after 2 hours of MV while connected to the isolated perfused mouse lung model setup. Exposure of liver endothelial cells to lung-derived mediators resulted in a significant increase in G-CSF, IL-6, CXCL-1, CXCL-2, and MCP-1 production compared to noncirculated control perfusate media (P<0.05). Furthermore, inhibition of the NF-κB pathway significantly mitigated this response. Changes in gene transcription were confirmed using qPCR for IL-6, CXCL-1, and CXCL-2. Additionally, liver tissue obtained from mice subjected to 2 hours of in vivo MV demonstrated significant increases in hepatic gene transcription of IL-6, CXCL-1, and CXCL-2 compared to nonventilated controls. Collectively, this data demonstrates that lung-derived mediators, generated in the setting of MV, are amplified by downstream organs in a feed forward mechanism of systemic inflammation. |
| format | Article |
| id | doaj-art-06f9a9ced8634ab8a1097b6d92c9ec02 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-06f9a9ced8634ab8a1097b6d92c9ec022025-02-03T05:58:48ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/586895586895Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent MechanismE. K. Patterson0L. J. Yao1N. Ramic2J. F. Lewis3G. Cepinskas4L. McCaig5R. A. W. Veldhuizen6C. M. Yamashita7Lawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaLawson Health Research Institute, London, ON, N6A 4V2, CanadaIn the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hypothesized that lung-derived mediators generated by mechanical ventilation (MV) are amplified by peripheral organs in a “feed forward” mechanism of systemic inflammation. Herein, lung-derived mediators were collected from 129X1/SVJ mice after 2 hours of MV while connected to the isolated perfused mouse lung model setup. Exposure of liver endothelial cells to lung-derived mediators resulted in a significant increase in G-CSF, IL-6, CXCL-1, CXCL-2, and MCP-1 production compared to noncirculated control perfusate media (P<0.05). Furthermore, inhibition of the NF-κB pathway significantly mitigated this response. Changes in gene transcription were confirmed using qPCR for IL-6, CXCL-1, and CXCL-2. Additionally, liver tissue obtained from mice subjected to 2 hours of in vivo MV demonstrated significant increases in hepatic gene transcription of IL-6, CXCL-1, and CXCL-2 compared to nonventilated controls. Collectively, this data demonstrates that lung-derived mediators, generated in the setting of MV, are amplified by downstream organs in a feed forward mechanism of systemic inflammation.http://dx.doi.org/10.1155/2013/586895 |
| spellingShingle | E. K. Patterson L. J. Yao N. Ramic J. F. Lewis G. Cepinskas L. McCaig R. A. W. Veldhuizen C. M. Yamashita Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism Mediators of Inflammation |
| title | Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism |
| title_full | Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism |
| title_fullStr | Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism |
| title_full_unstemmed | Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism |
| title_short | Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κB-Dependent Mechanism |
| title_sort | lung derived mediators induce cytokine production in downstream organs via an nf κb dependent mechanism |
| url | http://dx.doi.org/10.1155/2013/586895 |
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