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 24h. 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.
authors: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pecs, Szigeti Str. 12., H-7624 Pecs, Hungary.
authors: Krisztian
authors: K
authors: Elekes
authors: Katalin
authors: K
authors: Sandor
authors: Andras
authors: A
authors: Moricz
authors: Laszlo
authors: L
authors: Kereskai
authors: Agnes
authors: A
authors: Kemeny
authors: Eva
authors: E
authors: Szoke
authors: Aniko
authors: A
authors: Perkecz
authors: Dora
authors: D
authors: Reglodi
authors: Hitoshi
authors: H
authors: Hashimoto
authors: Erika
authors: E
authors: Pinter
authors: Janos
authors: J
authors: Szolcsanyi
authors: Zsuzsanna
authors: Z
authors: Helyes