Fig. 6. Netrin-1 dampens hypoxia-induced inflammation by enhancing extracellular adenosine signaling. During hypoxia-elicited inflammation of mucosal organs such as the lungs or the intestine, the transcription factor hypoxia-inducible factor (HIF) coordinates the induction of netrin-1. While originally described as a neuronal guidance molecule, recent studies implicate netrin-1 in the regulation of inflammatory responses. Here, epithelial-released netrin-1 dampens neutrophil accumulation in the hypoxic mucosa. This process involves activation of A2B adenosine receptor (AR)-dependent signaling pathways of neutrophils (alternative AR activation).