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Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights
Neurokinin-1 receptor blocking has been shown to be beneficial against lung injury in polymicrobial sepsis. In this paper, we evaluated the possible mediators and the mechanism involved. Mice were subjected to cecal ligation and puncture (CLP-) induced sepsis or sham surgery. Vehicle or SR140333 [1 ...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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SAGE-Hindawi Access to Research
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003979/ https://www.ncbi.nlm.nih.gov/pubmed/21188216 http://dx.doi.org/10.4061/2010/601098 |
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author | Hegde, Akhil Koh, Yung-Hua Moochhala, Shabbir M. Bhatia, Madhav |
author_facet | Hegde, Akhil Koh, Yung-Hua Moochhala, Shabbir M. Bhatia, Madhav |
author_sort | Hegde, Akhil |
collection | PubMed |
description | Neurokinin-1 receptor blocking has been shown to be beneficial against lung injury in polymicrobial sepsis. In this paper, we evaluated the possible mediators and the mechanism involved. Mice were subjected to cecal ligation and puncture (CLP-) induced sepsis or sham surgery. Vehicle or SR140333 [1 mg/kg; subcutaneous (s.c.)] was administered to septic mice either 30 min before or 1 h after the surgery. Lung tissue was collected 8 h after surgery and further analyzed. CLP alone caused a significant increase in the activation of the transcription factors, protein kinase C-α, extracellular signal regulated kinases, neurokinin receptors, and substance P levels in lung when compared to sham-operated mice. SR140333 injected pre- and post surgery significantly attenuated the activation of transcription factors and protein kinase C-α and the plasma levels of substance P compared to CLP-operated mice injected with the vehicle. In addition, GR159897 (0.12 mg/kg; s.c.), a neurokinin-2 receptor antagonist, failed to show beneficial effects. We conclude that substance P acting via neurokinin-1 receptor in sepsis initiated signaling cascade mediated mainly by protein kinase C-α, led to NF-κB and activator protein-1 activation, and further modulated proinflammatory mediators. |
format | Text |
id | pubmed-3003979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | SAGE-Hindawi Access to Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-30039792010-12-23 Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights Hegde, Akhil Koh, Yung-Hua Moochhala, Shabbir M. Bhatia, Madhav Int J Inflam Research Article Neurokinin-1 receptor blocking has been shown to be beneficial against lung injury in polymicrobial sepsis. In this paper, we evaluated the possible mediators and the mechanism involved. Mice were subjected to cecal ligation and puncture (CLP-) induced sepsis or sham surgery. Vehicle or SR140333 [1 mg/kg; subcutaneous (s.c.)] was administered to septic mice either 30 min before or 1 h after the surgery. Lung tissue was collected 8 h after surgery and further analyzed. CLP alone caused a significant increase in the activation of the transcription factors, protein kinase C-α, extracellular signal regulated kinases, neurokinin receptors, and substance P levels in lung when compared to sham-operated mice. SR140333 injected pre- and post surgery significantly attenuated the activation of transcription factors and protein kinase C-α and the plasma levels of substance P compared to CLP-operated mice injected with the vehicle. In addition, GR159897 (0.12 mg/kg; s.c.), a neurokinin-2 receptor antagonist, failed to show beneficial effects. We conclude that substance P acting via neurokinin-1 receptor in sepsis initiated signaling cascade mediated mainly by protein kinase C-α, led to NF-κB and activator protein-1 activation, and further modulated proinflammatory mediators. SAGE-Hindawi Access to Research 2010-09-20 /pmc/articles/PMC3003979/ /pubmed/21188216 http://dx.doi.org/10.4061/2010/601098 Text en Copyright © 2010 Akhil Hegde et al. https://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Article Hegde, Akhil Koh, Yung-Hua Moochhala, Shabbir M. Bhatia, Madhav Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title | Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title_full | Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title_fullStr | Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title_full_unstemmed | Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title_short | Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights |
title_sort | neurokinin-1 receptor antagonist treatment in polymicrobial sepsis: molecular insights |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003979/ https://www.ncbi.nlm.nih.gov/pubmed/21188216 http://dx.doi.org/10.4061/2010/601098 |
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