Substance P represents a novel first-line defense mechanism in the nose
(2018) In Journal of Allergy and Clinical Immunology 141(1). p.3-136- Abstract
Background: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. Objectives: We sought to examine the role of SP in nasal infection by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, with the latter reflected in changes in local Toll-like receptor (TLR) expression. Methods: The distribution of SP and TLRs in the nasal mucosa and local airway neurons was assessed with immunohistochemistry. The TLR7 agonists R-837 and R-848 were used to... (More)
Background: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. Objectives: We sought to examine the role of SP in nasal infection by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, with the latter reflected in changes in local Toll-like receptor (TLR) expression. Methods: The distribution of SP and TLRs in the nasal mucosa and local airway neurons was assessed with immunohistochemistry. The TLR7 agonists R-837 and R-848 were used to mimic a viral insult in the upper airways represented by primary human nasal epithelial cells (HNECs) and murine nasal epithelial cells (MNECs) and isolated murine trigeminal ganglial neurons. SP release from HNECs, MNECs, and trigeminal ganglial neurons was quantified with EIA. The effects of SP on TLR expression on HNECs were determined by using flow cytometry and confocal microscopy. Results: SP was released from the sensory neurons, MNECs, and HNECs within 15 minutes of local TLR7 stimulation. Subsequently, stimulation with SP induced upregulation of TLR expression in HNECs within 30 minutes through induction of TLR movement within HNECs. Upregulation of TLR expression was not evident when cells were treated with the neurokinin 1 receptor antagonist aprepitant before SP stimulation. Conclusions: This highlights a novel role for sensory neuropeptides as acute and local mediators of pathogen-driven inflammation, rapidly priming innate immune defenses in the airway.
(Less)
- author
- Larsson, Olivia ; Tengroth, Lotta ; Xu, Yuan ; Uddman, Rolf LU ; Kumlien Georén, Susanna and Cardell, Lars-Olaf LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Epithelial cells, Innate immunity, Nasal mucosa, Substance P, Toll-like receptor, Toll-like receptor 7, Viral infection
- in
- Journal of Allergy and Clinical Immunology
- volume
- 141
- issue
- 1
- pages
- 3 - 136
- publisher
- Elsevier
- external identifiers
-
- scopus:85019664752
- pmid:28219705
- ISSN
- 0091-6749
- DOI
- 10.1016/j.jaci.2017.01.021
- language
- English
- LU publication?
- yes
- id
- 713cd151-8e41-4043-bb7d-aa2562e11e14
- date added to LUP
- 2017-06-27 09:21:13
- date last changed
- 2024-03-31 12:03:06
@article{713cd151-8e41-4043-bb7d-aa2562e11e14,
abstract = {{<p>Background: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. Objectives: We sought to examine the role of SP in nasal infection by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, with the latter reflected in changes in local Toll-like receptor (TLR) expression. Methods: The distribution of SP and TLRs in the nasal mucosa and local airway neurons was assessed with immunohistochemistry. The TLR7 agonists R-837 and R-848 were used to mimic a viral insult in the upper airways represented by primary human nasal epithelial cells (HNECs) and murine nasal epithelial cells (MNECs) and isolated murine trigeminal ganglial neurons. SP release from HNECs, MNECs, and trigeminal ganglial neurons was quantified with EIA. The effects of SP on TLR expression on HNECs were determined by using flow cytometry and confocal microscopy. Results: SP was released from the sensory neurons, MNECs, and HNECs within 15 minutes of local TLR7 stimulation. Subsequently, stimulation with SP induced upregulation of TLR expression in HNECs within 30 minutes through induction of TLR movement within HNECs. Upregulation of TLR expression was not evident when cells were treated with the neurokinin 1 receptor antagonist aprepitant before SP stimulation. Conclusions: This highlights a novel role for sensory neuropeptides as acute and local mediators of pathogen-driven inflammation, rapidly priming innate immune defenses in the airway.</p>}},
author = {{Larsson, Olivia and Tengroth, Lotta and Xu, Yuan and Uddman, Rolf and Kumlien Georén, Susanna and Cardell, Lars-Olaf}},
issn = {{0091-6749}},
keywords = {{Epithelial cells; Innate immunity; Nasal mucosa; Substance P; Toll-like receptor; Toll-like receptor 7; Viral infection}},
language = {{eng}},
number = {{1}},
pages = {{3--136}},
publisher = {{Elsevier}},
series = {{Journal of Allergy and Clinical Immunology}},
title = {{Substance P represents a novel first-line defense mechanism in the nose}},
url = {{http://dx.doi.org/10.1016/j.jaci.2017.01.021}},
doi = {{10.1016/j.jaci.2017.01.021}},
volume = {{141}},
year = {{2018}},
}