RT Journal Article
SR Electronic
T1 Preventive and therapeutic treatment with a7 nicotinic receptor agonist reduced lung inflammation and collagen deposition in mice with acute lung injury
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3926
VO 44
IS Suppl 58
A1 Nathalia Pinheiro
A1 Fernanda Santana
A1 Marina Guerreiro
A1 Luciana Caperuto
A1 Iolanda Tiberio
A1 Vânia Prado
A1 Marco Antonio Prado
A1 Milton Martins
A1 Carla Prado
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P3926.abstract
AB Although cholinergic activity is involved in airway tone control, particularly by stimulation of muscarinic receptors, there is evidence that cholinergic anti-inflammatory pathway modulates immune systemic inflammatory responses in different models.Aim: We evaluated whether a7-nicotinic acetylcholine receptor (a7nAChR)stimulation reverted lung inflammation observed in an experimental model of acute lung injury (ALI).Methods:Male C57/BL6 mice received PNU-282987 (specificα7nAChRagonist) 30 min before (10 mg/kg, ip) or 6 hours after (2.5; 5 or 10 mg/kg) LPS administration (5 mg/kg, intratraqueal). We evaluated pulmonary mechanics, bronchoalveolar lavage fluid (BALF), collagen fibers and activation of NF-kBby immunohistochemistry and by Western Blotafter 24 hours from LPS.Results:After six hours, LPS treated animals presented increase in neutrophils and macrophages in BALF. Both pre and pos-treatment with PNU (10mg/Kg) reduced the total cells, macrophagesand neutrophilsin BALF (p<0.001 for all comparisons) as well as the NF-kB protein expression and positive cells (p<0.05) compared to LPS animals treated with vehicle. In addition, the PNU pretreatment attenuated the volume proportion of collagen fibers in lung tissue induced by LPS instillation (p<0.01) Conclusion: We concluded that a7 nAChRstimulation prevents and revertslung inflammation in a model of ALI probably by controlling NF-kB activation. Our data reinforced the idea that a7 nAChRis an important pathway to be better explored in the treatment of acute respiratory distress syndrome.