The neuropeptide substance P is a critical mediator of burn-induced acute lung injury
(2008) In Journal of immunology 180(12). p.41-8333- Abstract
The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses alter neural activity. Therefore, this study aimed to investigate the effect of local burn injury on inducing distant organ pulmonary SP release and its relevance to lung injury. Our results show that burn injury in male BALB/c mice subjected to 30% total body surface area full thickness burn augments significant production of SP,... (More)
The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses alter neural activity. Therefore, this study aimed to investigate the effect of local burn injury on inducing distant organ pulmonary SP release and its relevance to lung injury. Our results show that burn injury in male BALB/c mice subjected to 30% total body surface area full thickness burn augments significant production of SP, preprotachykinin-A gene expression, which encodes for SP, and biological activity of SP-neurokinin-1 receptor (NK1R) signaling. Furthermore, the enhanced SP-NK1R response correlates with exacerbated lung damage after burn as evidenced by increased microvascular permeability, edema, and neutrophil accumulation. The development of heightened inflammation and lung damage was observed along with increased proinflammatory IL-1beta, TNF-alpha, and IL-6 mRNA and protein production after injury in lung. Chemokines MIP-2 and MIP-1alpha were markedly increased, suggesting the active role of SP-induced chemoattractants production in trafficking inflammatory cells. More importantly, administration of L703606, a specific NK1R antagonist, 1 h before burn injury significantly disrupted the SP-NK1R signaling and reversed pulmonary inflammation and injury. The present findings show for the first time the role of SP in contributing to exaggerated pulmonary inflammatory damage after burn injury via activation of NK1R signaling.
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- author
- Sio, Selena Wei Shan ; Puthia, Manoj Kumar LU ; Lu, Jia ; Moochhala, Shabbir and Bhatia, Madhav
- publishing date
- 2008-06-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acute Disease, Adjuvants, Immunologic/biosynthesis, Animals, Blood Platelets/pathology, Burns/blood, Capillary Permeability/immunology, Chemokines/biosynthesis, Cytokines/biosynthesis, Disease Models, Animal, Inflammation Mediators/blood, Lung/immunology, Lymphocytes/pathology, Male, Mice, Mice, Inbred BALB C, Monocytes/pathology, Neutrophils/pathology, RNA, Messenger/biosynthesis, Receptors, Neurokinin-1/blood, Signal Transduction/immunology, Substance P/biosynthesis
- in
- Journal of immunology
- volume
- 180
- issue
- 12
- pages
- 9 pages
- publisher
- American Association of Immunologists
- external identifiers
-
- scopus:50949125139
- pmid:18523300
- ISSN
- 0022-1767
- DOI
- 10.4049/jimmunol.180.12.8333
- language
- English
- LU publication?
- no
- id
- c4c32f6c-7ea9-490d-ada8-1a199c05e650
- date added to LUP
- 2018-08-27 13:42:22
- date last changed
- 2024-06-24 18:12:32
@article{c4c32f6c-7ea9-490d-ada8-1a199c05e650,
abstract = {{<p>The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses alter neural activity. Therefore, this study aimed to investigate the effect of local burn injury on inducing distant organ pulmonary SP release and its relevance to lung injury. Our results show that burn injury in male BALB/c mice subjected to 30% total body surface area full thickness burn augments significant production of SP, preprotachykinin-A gene expression, which encodes for SP, and biological activity of SP-neurokinin-1 receptor (NK1R) signaling. Furthermore, the enhanced SP-NK1R response correlates with exacerbated lung damage after burn as evidenced by increased microvascular permeability, edema, and neutrophil accumulation. The development of heightened inflammation and lung damage was observed along with increased proinflammatory IL-1beta, TNF-alpha, and IL-6 mRNA and protein production after injury in lung. Chemokines MIP-2 and MIP-1alpha were markedly increased, suggesting the active role of SP-induced chemoattractants production in trafficking inflammatory cells. More importantly, administration of L703606, a specific NK1R antagonist, 1 h before burn injury significantly disrupted the SP-NK1R signaling and reversed pulmonary inflammation and injury. The present findings show for the first time the role of SP in contributing to exaggerated pulmonary inflammatory damage after burn injury via activation of NK1R signaling.</p>}},
author = {{Sio, Selena Wei Shan and Puthia, Manoj Kumar and Lu, Jia and Moochhala, Shabbir and Bhatia, Madhav}},
issn = {{0022-1767}},
keywords = {{Acute Disease; Adjuvants, Immunologic/biosynthesis; Animals; Blood Platelets/pathology; Burns/blood; Capillary Permeability/immunology; Chemokines/biosynthesis; Cytokines/biosynthesis; Disease Models, Animal; Inflammation Mediators/blood; Lung/immunology; Lymphocytes/pathology; Male; Mice; Mice, Inbred BALB C; Monocytes/pathology; Neutrophils/pathology; RNA, Messenger/biosynthesis; Receptors, Neurokinin-1/blood; Signal Transduction/immunology; Substance P/biosynthesis}},
language = {{eng}},
month = {{06}},
number = {{12}},
pages = {{41--8333}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{The neuropeptide substance P is a critical mediator of burn-induced acute lung injury}},
url = {{http://dx.doi.org/10.4049/jimmunol.180.12.8333}},
doi = {{10.4049/jimmunol.180.12.8333}},
volume = {{180}},
year = {{2008}},
}