Lipopolysaccharide induces epithelium- and prostaglandin E(2)-dependent relaxation of mouse isolated trachea through activation of cyclooxygenase (COX)-1 and COX-2.

Lipopolysaccharide (LPS), a Toll-like receptor (TLR) 4 agonist, causes airway hyperreactivity through nuclear factor-kappaB (NF-kappaB). Because NF-kappaB induces cyclooxygenase-2 (COX-2) to increase synthesis of prostaglandins (PGs), including the potent airway anti-inflammatory and smooth muscle relaxant PGE(2), we investigated whether LPS causes short-term PGE(2)-dependent relaxation of mouse isolated trachea. In rings of trachea contracted submaximally with carbachol, LPS caused slowly developing, epithelium-dependent relaxations that reached a maximum within 60 min.

Protease-activated receptor-2 peptides activate neurokinin-1 receptors in the mouse isolated trachea.

Protective roles for protease-activated receptor-2 (PAR(2)) in the airways including activation of epithelial chloride (Cl(-)) secretion are based on the use of presumably PAR(2)-selective peptide agonists. To determine whether PAR(2) peptide-activated Cl(-) secretion from mouse tracheal epithelium is dependent on PAR(2), changes in ion conductance across the epithelium [short-circuit current (I(SC))] to PAR(2) peptides were measured in Ussing chambers under voltage clamp. In addition, epithelium- and endothelium-dependent relaxations to these peptides were measured in two established PAR(2) bioassays, isolated ring segments of mouse trachea and rat thoracic aorta, respectively.