Potential pro- and anti-inflammatory actions of prostanoids in asthma. (a) Proinflammatory actions of TXA₂ and PGE₂. Solid red receptors indicate pathways that enhance airway inflammation. TXA₂ activates leukocytes and increases airway obstruction by inducing airway smooth muscle contraction and goblet cell mucus secretion. PGE₂ promotes vasodilation by activating cAMP-coupled EP2 receptors on vascular smooth muscle and increases vascular permeability indirectly by enhancing the release of histamine and other mediators from tissue leukocytes such as mast cells. Receptors for which there is insufficient information to define a proinflammatory role are depicted in gray. (b) Anti-inflammatory actions of PGE₂. Solid blue receptors indicate pathways that reduce airway inflammation. As inflammation progresses, PGE₂ synthesis by macrophages is enhanced due to increased expression of COX-2 and PGE-synthase. PGE₂ inhibits leukocyte activation and promotes bronchodilation through activation of G_s-coupled EP2 and EP4 receptors. Increased expression of EP2 receptors is likely to further enhance these anti-inflammatory actions of PGE₂. Receptors for which there is insufficient information to define an anti-inflammatory role are depicted in gray. H1, histamine receptor; TP, TXA₂ receptor; EP, PGE₂ receptor.