LPA and Autotaxin: Potential Drug Targets in Asthma?

Lysophosphatidic acid (LPA) is a versatile lysolipid, and activates a variety of signaling cascades in many cell types. Extracellular LPA is produced from lysophosphatidylcholine (LPC) by the enzyme autotaxin (ATX), and binds to a family of G-protein coupled receptors on its target cells. Research by many groups continues to support the idea that LPA, and the ATX-LPA axis, have important roles in asthma and allergic airway inflammation. In vitro studies have shown that LPA activates many cell types implicated in airway inflammation, including eosinophils, mast cells, dendritic cells, lymphocytes, airway epithelial cells, and airway smooth muscle cells. In animal models ATX and LPA receptor antagonists have been shown to attenuate allergic airway inflammation and hyperreactivity, cardinal features of asthma in humans. ATX and LPA antagonists are currently under active development to treat lung fibrosis, cancer, and other conditions. If compounds with acceptable safety profiles can be identified, then it seems likely that they will be useful in inflammatory lung diseases like asthma.