The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function.

Rochlitzer, S., Veres, T.Z,, Kühne, K., Prenzler, F., Pilzner, C., Knothe, S., Winkler, C., Lauenstein, H.D., Willart, M., Hammad, H., Müller, M., Krug, N., Lambrecht, B.N., Braun, A.
Journal   Clin Exp Allergy.
Species  
Analytes Measured   IL-10 , IL-2 , IL-4 , IL-5
Matrix Tested   Bronchoalveolar lavage (BAL) fluid, Lymph node cell culture supernatants
Year   2011
Volume   41
Page Numbers   1609-1621
Application   Cytokines and Chemokines
Abstract
BACKGROUND: The neuropeptide calcitonin gene-related peptide (CGRP) is released in the lung by sensory nerves during allergic airway responses. Pulmonary dendritic cells (DC) orchestrating the allergic inflammation could be affected by CGRP.

OBJECTIVE: To determine the immunomodulatory effects of CGRP on DC function and its impact on the induction of allergic airway inflammation.

METHODS: CGRP receptor expression on lung DC was determined by RT-PCR and immunofluorescence staining. The functional consequences of CGRP receptor triggering were evaluated in vitro using bone marrow-derived DC. DC maturation and the induction of ovalbumin (OVA)-specific T cell responses were analysed by flow cytometry. The in vivo relevance of the observed DC modulation was assessed in a DC-transfer model of experimental asthma. Mice were sensitized by an intrapharyngeal transfer of OVA-pulsed DC and challenged with OVA aerosol. The impact of CGRP pretreatment of DC on airway inflammation was characterized by analysing differential cell counts and cytokines in bronchoalveolar lavage fluid (BALF), lung histology and cytokine responses in mediastinal lymph nodes.

RESULTS: RT-PCR, immunofluorescence and cAMP assay demonstrated the expression of functionally active CGRP receptors in lung DC. RT-PCR revealed a transcriptional CGRP receptor down-regulation during airway inflammation. CGRP specifically inhibited the maturation of in vitro generated DC. Maturation was restored by blocking with the specific antagonist CGRP(8-37) . Consequently, CGRP-pretreated DC reduced the activation and proliferation of antigen-specific T cells and induced increased the numbers of T regulatory cells. The transfer of CGRP-pretreated DC diminished allergic airway inflammation in vivo, shown by reduced eosinophil numbers and increased levels of IL-10 in BALF.

CONCLUSIONS AND CLINICAL RELEVANCE: CGRP inhibits DC maturation and allergen-specific T cell responses, which affects the outcome of the allergic airway inflammation in vivo. This suggests an additional mechanism by which nerve-derived mediators interfere with local immune responses. Thus, CGRP as an anti-inflammatory mediator could represent a new therapeutic tool in asthma therapy.

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Multiplex
V-PLEX Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-2 Antibody
IL-2
Human IL-4 Antibody
IL-4
Human IL-5 Antibody
IL-5
Human IL-10 Antibody
IL-10
Mouse IL-2 Antibody
IL-2
Mouse IL-4 Antibody
IL-4
Mouse IL-5 Antibody
IL-5
Mouse IL-10 Antibody
IL-10
Rat IL-4 Antibody
IL-4
Rat IL-5 Antibody
IL-5
Rat IL-10 Antibody
IL-10
V-PLEX Cytokine Panel 1 Human Kit
GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-2 Kit
IL-2 | Human
Singleplex
V-PLEX Human IL-5 Kit
IL-5 | Human
Singleplex
V-PLEX Human IL-10 Kit
IL-10 | Human
Singleplex
V-PLEX Mouse IL-2 Kit
IL-2 | Mouse
Singleplex
V-PLEX Mouse IL-4 Kit
IL-4 | Mouse
Singleplex
V-PLEX Mouse IL-5 Kit
IL-5 | Mouse
Singleplex
V-PLEX Mouse IL-10 Kit
IL-10 | Mouse
Singleplex
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