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

Krisztian Elekes, Katalin Sandor, Andras Moricz, Laszlo Kereskai, Agnes Kemeny, Eva Szoke, Aniko Perkecz, Dora Reglodi, Hitoshi Hashimoto, Erika Pinter, Janos Szolcsanyi, Zsuzsanna Helyes

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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