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

(2011) CLINICAL AND EXPERIMENTAL ALLERGY. 41(11). p.1609-1621
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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.
Keywords
calcitonin gene-related peptide, neuro-immune interactions, allergic asthma, dendritic cells, sensory nerves, INHALED ANTIGEN, SENSORY NERVES, SUBSTANCE-P, BONE-MARROW, MOUSE MODEL, IN-VIVO, ASTHMA, RESPONSES, MICE, EXPRESSION

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MLA
Rochlitzer, S., et al. “The Neuropeptide Calcitonin Gene-Related Peptide Affects Allergic Airway Inflammation by Modulating Dendritic Cell Function.” CLINICAL AND EXPERIMENTAL ALLERGY, vol. 41, no. 11, 2011, pp. 1609–21, doi:10.1111/j.1365-2222.2011.03822.x.
APA
Rochlitzer, S., Veres, T., Kühne, K., Prenzler, F., Pilzner, C., Knothe, S., … Braun, A. (2011). The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function. CLINICAL AND EXPERIMENTAL ALLERGY, 41(11), 1609–1621. https://doi.org/10.1111/j.1365-2222.2011.03822.x
Chicago author-date
Rochlitzer, S, TZ Veres, K Kühne, F Prenzler, C Pilzner, S Knothe, C Winkler, et al. 2011. “The Neuropeptide Calcitonin Gene-Related Peptide Affects Allergic Airway Inflammation by Modulating Dendritic Cell Function.” CLINICAL AND EXPERIMENTAL ALLERGY 41 (11): 1609–21. https://doi.org/10.1111/j.1365-2222.2011.03822.x.
Chicago author-date (all authors)
Rochlitzer, S, TZ Veres, K Kühne, F Prenzler, C Pilzner, S Knothe, C Winkler, HD Lauenstein, Monique Willart, Hamida Hammad, M Müller, N Krug, Bart Lambrecht, and A Braun. 2011. “The Neuropeptide Calcitonin Gene-Related Peptide Affects Allergic Airway Inflammation by Modulating Dendritic Cell Function.” CLINICAL AND EXPERIMENTAL ALLERGY 41 (11): 1609–1621. doi:10.1111/j.1365-2222.2011.03822.x.
Vancouver
1.
Rochlitzer S, Veres T, Kühne K, Prenzler F, Pilzner C, Knothe S, et al. The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function. CLINICAL AND EXPERIMENTAL ALLERGY. 2011;41(11):1609–21.
IEEE
[1]
S. Rochlitzer et al., “The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function,” CLINICAL AND EXPERIMENTAL ALLERGY, vol. 41, no. 11, pp. 1609–1621, 2011.
@article{1996948,
  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.}},
  author       = {{Rochlitzer, S and Veres, TZ and Kühne, K and Prenzler, F and Pilzner, C and Knothe, S and Winkler, C and Lauenstein, HD and Willart, Monique and Hammad, Hamida and Müller, M and Krug, N and Lambrecht, Bart and Braun, A}},
  issn         = {{0954-7894}},
  journal      = {{CLINICAL AND EXPERIMENTAL ALLERGY}},
  keywords     = {{calcitonin gene-related peptide,neuro-immune interactions,allergic asthma,dendritic cells,sensory nerves,INHALED ANTIGEN,SENSORY NERVES,SUBSTANCE-P,BONE-MARROW,MOUSE MODEL,IN-VIVO,ASTHMA,RESPONSES,MICE,EXPRESSION}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1609--1621}},
  title        = {{The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function}},
  url          = {{http://doi.org/10.1111/j.1365-2222.2011.03822.x}},
  volume       = {{41}},
  year         = {{2011}},
}

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