Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation: In vivo study with gene-deleted mice

K. Elekes, K. Sándor, Andras Moricz, L. Kereskai, Agnes Kemeny, E. Szöke, Aniko Perkecz, D. Reglodi, Hitoshi Hashimoto, E. Pintér, J. Szolcsányi, Z. Helyes

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Abstract

The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in capsaicin-sensitive peptidergic sensory nerves, inflammatory and immune cells suggest its involvement in inflammation. However, data on its role in different inflammatory processes are contradictory and there is little known about its functions in the airways. Therefore, our aim was to examine intranasal endotoxin-induced subacute airway inflammation in PACAP gene-deficient (PACAP-/-) and wild-type (PACAP+/+) mice. Airway responsiveness to inhaled carbachol was determined in unrestrained mice with whole body plethysmography 6 h and 24 h after LPS. Myeloperoxidase (MPO) activity referring to the number of accumulated neutrophils and macrophages was measured with spectrophotometry and interleukin-1β (IL-1β) concentration with ELISA from the lung homogenates. Histological evaluation and semiquantitative scoring were also performed. Bronchial responsiveness, as well as IL-1β concentration and MPO activity markedly increased at both timepoints. Perivascular edema dominated the histological picture at 6 h, while remarkable peribronchial granulocyte accumulation, macrophage infiltration and goblet cell hyperplasia were seen at 24 h. In PACAP-/- mice, airway hyperreactivity was significantly higher 24 h after LPS and inflammatory histopathological changes were more severe at both timepoints. MPO increase was almost double in PACAP-/- mice compared to the wild-types at 6 h. In contrast, there was no difference between the IL-1β concentrations of the PACAP+/+ and PACAP-/- mice. These results provide evidence for a protective role for PACAP in endotoxin-induced airway inflammation and hyperreactivity.

Original languageEnglish
Pages (from-to)1439-1446
Number of pages8
JournalPeptides
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Pituitary Adenylate Cyclase-Activating Polypeptide
Endotoxins
Anti-Inflammatory Agents
Genes
Inflammation
Interleukin-1
Peroxidase
Macrophages
Whole Body Plethysmography
Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Plethysmography
Goblet Cells
Spectrophotometry
Capsaicin
Carbachol
Infiltration
Granulocytes
Hyperplasia
Edema
Neutrophils

Keywords

  • Airway hyperresponsiveness
  • Enhanced pause (Penh)
  • Interleukin-1β
  • Lipopolysaccharide
  • Myeloperoxidase activity
  • Whole body plethysmography

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

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title = "Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation: In vivo study with gene-deleted mice",
abstract = "The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in capsaicin-sensitive peptidergic sensory nerves, inflammatory and immune cells suggest its involvement in inflammation. However, data on its role in different inflammatory processes are contradictory and there is little known about its functions in the airways. Therefore, our aim was to examine intranasal endotoxin-induced subacute airway inflammation in PACAP gene-deficient (PACAP-/-) and wild-type (PACAP+/+) mice. Airway responsiveness to inhaled carbachol was determined in unrestrained mice with whole body plethysmography 6 h and 24 h after LPS. Myeloperoxidase (MPO) activity referring to the number of accumulated neutrophils and macrophages was measured with spectrophotometry and interleukin-1β (IL-1β) concentration with ELISA from the lung homogenates. Histological evaluation and semiquantitative scoring were also performed. Bronchial responsiveness, as well as IL-1β concentration and MPO activity markedly increased at both timepoints. Perivascular edema dominated the histological picture at 6 h, while remarkable peribronchial granulocyte accumulation, macrophage infiltration and goblet cell hyperplasia were seen at 24 h. In PACAP-/- mice, airway hyperreactivity was significantly higher 24 h after LPS and inflammatory histopathological changes were more severe at both timepoints. MPO increase was almost double in PACAP-/- mice compared to the wild-types at 6 h. In contrast, there was no difference between the IL-1β concentrations of the PACAP+/+ and PACAP-/- mice. These results provide evidence for a protective role for PACAP in endotoxin-induced airway inflammation and hyperreactivity.",
keywords = "Airway hyperresponsiveness, Enhanced pause (Penh), Interleukin-1β, Lipopolysaccharide, Myeloperoxidase activity, Whole body plethysmography",
author = "K. Elekes and K. S{\'a}ndor and Andras Moricz and L. Kereskai and Agnes Kemeny and E. Sz{\"o}ke and Aniko Perkecz and D. Reglodi and Hitoshi Hashimoto and E. Pint{\'e}r and J. Szolcs{\'a}nyi and Z. Helyes",
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T1 - Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation

T2 - In vivo study with gene-deleted mice

AU - Elekes, K.

AU - Sándor, K.

AU - Moricz, Andras

AU - Kereskai, L.

AU - Kemeny, Agnes

AU - Szöke, E.

AU - Perkecz, Aniko

AU - Reglodi, D.

AU - Hashimoto, Hitoshi

AU - Pintér, E.

AU - Szolcsányi, J.

AU - Helyes, Z.

PY - 2011/7

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N2 - The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in capsaicin-sensitive peptidergic sensory nerves, inflammatory and immune cells suggest its involvement in inflammation. However, data on its role in different inflammatory processes are contradictory and there is little known about its functions in the airways. Therefore, our aim was to examine intranasal endotoxin-induced subacute airway inflammation in PACAP gene-deficient (PACAP-/-) and wild-type (PACAP+/+) mice. Airway responsiveness to inhaled carbachol was determined in unrestrained mice with whole body plethysmography 6 h and 24 h after LPS. Myeloperoxidase (MPO) activity referring to the number of accumulated neutrophils and macrophages was measured with spectrophotometry and interleukin-1β (IL-1β) concentration with ELISA from the lung homogenates. Histological evaluation and semiquantitative scoring were also performed. Bronchial responsiveness, as well as IL-1β concentration and MPO activity markedly increased at both timepoints. Perivascular edema dominated the histological picture at 6 h, while remarkable peribronchial granulocyte accumulation, macrophage infiltration and goblet cell hyperplasia were seen at 24 h. In PACAP-/- mice, airway hyperreactivity was significantly higher 24 h after LPS and inflammatory histopathological changes were more severe at both timepoints. MPO increase was almost double in PACAP-/- mice compared to the wild-types at 6 h. In contrast, there was no difference between the IL-1β concentrations of the PACAP+/+ and PACAP-/- mice. These results provide evidence for a protective role for PACAP in endotoxin-induced airway inflammation and hyperreactivity.

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